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958 Publications visible to you, out of a total of 958
Obesity Associated Cerebral Gray and White Matter Alterations Are Interrelated in the Female Brain.
LIFE Adult

Abstract (Expand)

Obesity is known to affect the brain's gray matter (GM) and white matter (WM) structure but the interrelationship of such changes remains unclear. Here we used T1-weighted magnetic resonance imaging … (MRI) in combination with voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) with tract-based spatial statistics (TBSS) to assess the relationship between obesity-associated alterations of gray matter density (GMD) and anisotropic water diffusion in WM, respectively. In a small cohort of lean to obese women, we confirmed previous reports of obesity-associated alterations of GMD in brain regions involved in executive control (i.e., dorsolateral prefrontal cortex, DLPFC) and habit learning (i.e., dorsal striatum). Gray matter density alterations of the DLPFC were negatively correlated with radial diffusivity in the entire corpus callosum. Within the genu of the corpus callosum we found a positive correlation with axial diffusivity. In posterior region and inferior areas of the body of the corpus callosum, axial diffusivity correlated negatively with altered GMD in the dorsal striatum. These findings suggest that, in women, obesity-related alterations of GMD in brain regions involved in executive control and habit learning might relate to alterations of associated WM fiber bundles within the corpus callosum.

Authors: K. Mueller, A. Horstmann, H. E. Moller, A. Anwander, J. Lepsien, M. L. Schroeter, A. Villringer, B. Pleger

Date Published: 11th Dec 2014

Publication Type: Not specified

Human Diseases: obesity

Obesity is Associated with White Matter Changes and Cognitions among Healthy Elderly
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Midlife obesity has often been associated with accelerated cognitive decline during aging. Obesity leads to changes in multiple physiological factors that could impact neuronal tissue. Numerous studies … have linked obesity and higher body mass index (BMI) with differences in cognitive functions and brain structure, including total brain volume, regional gray matter volume and white matter (WM) microstructure. However, regarding to WM, the available neuroimaging studies incorporated mainly small sample sizes that yielded less conclusive results. Thus, we investigated the association of obesity, measured using BMI and waist to hip ratio (WHR), with changes in WM microstructure, as well as variance in cognitive test scores in a large cohort of community-dwelling healthy individuals older than 60 years.

Authors: Rui Zhang, L. Lampe, Frauke Beyer, Sebastian Huhn, S. K. Masouleh, T. Luck, S. G. Riedel-Heller, Markus Löffler, M. L. Schroeter

Date Published: 28th Nov 2016

Publication Type: Not specified

Human Diseases: obesity

Obesity negatively impacts outcome in elderly female patients with aggressive B-cell lymphomas treated with R-CHOP: results from prospective trials of the German high grade non-Hodgkin's lymphoma trial group.
GLA - German Lymphoma Alliance

Abstract (Expand)

To study if obesity is a risk factor in elderly patients (>60 years) with aggressive B-cell lymphoma, the outcomes of 576 elderly patients treated with rituximab in the RICOVER-60 trial were analysed … in a retrospective study with regard to body mass index (BMI) and gender. Of the 576 patients, 1% had low body weight (BMI < 18.5), 38% were normal weight (18.5 </= BMI < 25), 42% were overweight (25 </= BMI < 30) and 19% were obese (BMI >/= 30). Event-free (EFS), progression-free (PFS) and overall survival (OS) according to BMI showed no significant differences for all and for male patients. EFS (P = 0.041), PFS (P = 0.038) and OS (P = 0.031) were significantly better for female non-obese patients. A multivariate analysis adjusted for International Prognostic Index risk factors confirmed these results, with the following hazard ratios (HR) for obesity (BMI >/= 30) for EFS/PFS/OS: all patients - 1.4/1.4/1.4 (not significant); male patients - 1.2/1.2/1.0 (not significant) and female patients - 1.7 (P = 0.032)/1.9 (P = 0.022)/2.0 (P = 0.017). In conclusion, obesity is a risk factor that influences treatment outcome in elderly female patients with aggressive B-cell lymphoma treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone). The inferior outcomes in obese female patients may be due to faster rituximab clearance in obese females.

Authors: K. Hohloch, B. Altmann, M. Pfreundschuh, M. Loeffler, N. Schmitz, F. Zettl, M. Ziepert, L. Trumper

Date Published: 2nd Dec 2017

Publication Type: Not specified

Human Diseases: obesity, B-cell lymphoma

Ökonomische Effekte aus teleradiologischen Anwendungen zwischen stationären und ambulanten Leistungserbringern am Beispiel von SaxTelemed
Management of health information systems

Abstract

Not specified

Authors: G. Haufe, O. Schlimpert, P. Groh, K. Möser, Alfred Winter

Date Published: 2003

Publication Type: Journal article

Olfactory dysfunction: properties of the Sniffin' Sticks Screening 12 test and associations with quality of life.
LIFE Adult

Abstract (Expand)

PURPOSE: The Sniffin' Sticks Screening 12 test is a test of olfactory performance based on pen-like odor dispensing devices. The aims of this study were to analyze the performance of this test in … a general population sample and to explore associations between olfactory dysfunction and quality of life. METHODS: A large community sample (n = 7267) completed the Sniffin' Sticks Screening 12 test and several questionnaires measuring quality of life, anxiety, dispositional optimism, social support, and satisfaction with life. RESULTS: According to the criteria recommended by the test manufacturer, 5.1% of the participants were anosmic (score </= 6), 52.4% were dysosmic (7 </= score </= 10), and 42.5% were normosmic (score >/= 11). While frequencies of correct identification differed between the 12 sticks, all sticks contributed positively to the test results. The associations between olfactory functioning and quality of life variables were negligible. In the multivariate analyses, none of the associations reached the 1% significance level. CONCLUSIONS: While studies with patients in otorhinolaryngological clinics often report substantial detriments to their quality of life in relation to olfactory dysfunction, the present epidemiological study cannot confirm this association for the general population.

Authors: A. Hinz, T. Luck, S. G. Riedel-Heller, P. Y. Herzberg, C. Rolffs, K. Wirkner, C. Engel

Date Published: 21st Nov 2018

Publication Type: Not specified

Olfactory function is associated with cognitive performance: results from the population-based LIFE-Adult-Study.
LIFE Adult

Abstract (Expand)

BACKGROUND: Studies in older adults or those with cognitive impairment have shown associations between cognitive and olfactory performance, but there are few population-based studies especially in … younger adults. We therefore cross-sectionally analyzed this association using data from the population-based LIFE-Adult-Study. METHODS: Cognitive assessments comprised tests from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD): verbal fluency (VF), word list learning and recall (WLL, WLR), and the Trail Making Tests (TMT) A and B. The "Sniffin' Sticks Screening 12" test was used to measure olfactory performance. Linear regression analyses were performed to determine associations between the number of correctly identified odors (0 to 12) and the five cognitive test scores, adjusted for sex, age, education, and the presence of depressive symptoms. Receiver operating characteristic (ROC) analysis was carried out to determine the discriminative performance of the number of correctly identified odors regarding identification of cognition impairment. RESULTS: A total of 6783 participants (51.3% female) completed the olfaction test and the VF test and TMT. A subgroup of 2227 participants (46.9% female) also completed the WLL and WLR tests. Based on age-, sex-, and education-specific norms from CERAD, the following numbers of participants were considered cognitively impaired: VF 759 (11.2%), WLL 242 (10.9%), WLR: 132 (5.9%), TMT-A 415 (6.1%), and TMT-B/A ratio 677 (10.0%). On average, score values for VF were higher by 0.42 points (p < 0.001), for WLL higher by 0.32 points (p = 0.001), for WLR higher by 0.31 points (p = 0.002), for TMT-A lower by 0.25 points (p < 0.001), and for TMT-B/A ratio lower by 0.01 points (p < 0.001) per number of correctly identified odors. ROC analysis revealed area under the curve values from 0.55 to 0.62 for the five cognitive tests. CONCLUSIONS: Better olfactory performance was associated with better cognitive performance in all five tests in adults - adjusted for age, sex, education, and the presence of depressive symptoms. However, the ability of the smell test to discriminate between individuals with and without cognitive impairment was limited. The value of olfactory testing in early screening for cognitive impairment should be investigated in longitudinal studies.

Authors: M. Yahiaoui-Doktor, T. Luck, S. G. Riedel-Heller, M. Loeffler, K. Wirkner, C. Engel

Date Published: 10th May 2019

Publication Type: Not specified

Human Diseases: Alzheimer's disease

On Teaching International Courses on Health Information Systems: Lessons Learned during 16 Years of Frank - van Swieten Lectures on Strategic Information Management in Health Information Systems
Management of health information systems

Abstract

Not specified

Authors: Elske Ammenwerth, Petra Knaup-Gregori, Alfred Winter, A.W. Bauer, O.J. Bott, M. Gietzelt, B. Haarbrandt, W.O. Hackl, N. Hellrung, G. Hübner-Bloder, Franziska Jahn, M.W. Jaspers, U. Kutscha, C. Machan, B. Oppermann, J. Pilz, J. Schwartze, C. Seidel, J.E. Slot, S. Smers, K. Spitalewski, N. Steckel, Alexander Strübing, M. van der Haak, Reinhold Haux, W.J. ter Burg

Date Published: 31st Jan 2018

Publication Type: Journal article

On the Conditional Power in Survival Time Analysis Considering Cure Fractions.
Genetical Statistics and Systems Biology

Abstract (Expand)

Conditional power of survival endpoints at interim analyses can support decisions on continuing a trial or stopping it for futility. When a cure fraction becomes apparent, conditional power cannot be … calculated accurately using simple survival models, e.g. the exponential model. Non-mixture models consider such cure fractions. In this paper, we derive conditional power functions for non-mixture models, namely the non-mixture exponential, the non-mixture Weibull, and the non-mixture Gamma models. Formulae were implemented in the R package CP. For an example data set of a clinical trial, we calculated conditional power under the non-mixture models and compared results with those under the simple exponential model.

Authors: A. Kuehnapfel, F. Schwarzenberger, M. Scholz

Date Published: 17th Mar 2017

Publication Type: Journal article

On the Cooperation between Epigenetics and Transcription Factor Networks in the Specification of Tissue Stem Cells
LHA - Leipzig Health Atlas

Abstract (Expand)

It is generally accepted that epigenetic modifications, such as DNA and histone methylations, affect transcription and that a gene’s transcription feeds back on its epigenetic profile. Depending on the … epigenetic modification, positive and negative feedback loops have been described. Here, we study whether such interrelation are mandatory and how transcription factor networks affect it. We apply self-organizing map machine learning to a published data set on the specification and differentiation of murine intestinal stem cells in order to provide an integrative view of gene transcription and DNA, as well as histone methylation during this process. We show that, although gain/loss of H3K4me3 at a gene promoter is generally considered to be associated with its increased/decreased transcriptional activity, such an interrelation is not mandatory, i.e., changes of the modification level do not necessarily affect transcription. Similar considerations hold for H3K27me3. In addition, even strong changes in the transcription of a gene do not necessarily affect its H3K4me3 and H3K27me3 modification profile. We provide a mechanistic explanation of these phenomena that is based on a model of epigenetic regulation of transcription. Thereby, the analyzed data suggest a broad variance in gene specific regulation of histone methylation and support the assumption of an independent regulation of transcription by histone methylation and transcription factor networks. The results provide insights into basic principles of the specification of tissue stem cells and highlight open questions about a mechanistic modeling of this process.

Authors: T. Thalheim, Lydia Hopp, Hans Binder, G. Aust, J. Galle

Date Published: No date defined

Publication Type: Not specified

On the impact of relatedness on SNP association analysis
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND When testing for SNP (single nucleotide polymorphism) associations in related individuals, observations are not independent. Simple linear regression assuming independent normally distributed …d residuals results in an increased type I error and the power of the test is also affected in a more complicate manner. Inflation of type I error is often successfully corrected by genomic control. However, this reduces the power of the test when relatedness is of concern. In the present paper, we derive explicit formulae to investigate how heritability and strength of relatedness contribute to variance inflation of the effect estimate of the linear model. Further, we study the consequences of variance inflation on hypothesis testing and compare the results with those of genomic control correction. We apply the developed theory to the publicly available HapMap trio data (N=129), the Sorbs (a self-contained population with N=977 characterised by a cryptic relatedness structure) and synthetic family studies with different sample sizes (ranging from N=129 to N=999) and different degrees of relatedness. RESULTS We derive explicit and easily to apply approximation formulae to estimate the impact of relatedness on the variance of the effect estimate of the linear regression model. Variance inflation increases with increasing heritability. Relatedness structure also impacts the degree of variance inflation as shown for example family structures. Variance inflation is smallest for HapMap trios, followed by a synthetic family study corresponding to the trio data but with larger sample size than HapMap. Next strongest inflation is observed for the Sorbs, and finally, for a synthetic family study with a more extreme relatedness structure but with similar sample size as the Sorbs. Type I error increases rapidly with increasing inflation. However, for smaller significance levels, power increases with increasing inflation while the opposite holds for larger significance levels. When genomic control is applied, type I error is preserved while power decreases rapidly with increasing variance inflation. CONCLUSIONS Stronger relatedness as well as higher heritability result in increased variance of the effect estimate of simple linear regression analysis. While type I error rates are generally inflated, the behaviour of power is more complex since power can be increased or reduced in dependence on relatedness and the heritability of the phenotype. Genomic control cannot be recommended to deal with inflation due to relatedness. Although it preserves type I error, the loss in power can be considerable. We provide a simple formula for estimating variance inflation given the relatedness structure and the heritability of a trait of interest. As a rule of thumb, variance inflation below 1.05 does not require correction and simple linear regression analysis is still appropriate.

Authors: Arnd Gross, Anke Tönjes, Markus Scholz

Date Published: 1st Dec 2017

Publication Type: Journal article

On the necessity of Mobile Information Processing in Hospitals
Management of health information systems

Abstract

Not specified

Authors: R. Werner, Reinhold Haux, F. Leiner, Alfred Winter

Date Published: 1994

Publication Type: InCollection

On the Parametrization of Epidemiologic Models-Lessons from Modelling COVID-19 Epidemic.
Genetical Statistics and Systems Biology, Task Force COVID-19 Leipzig

Abstract (Expand)

Numerous prediction models of SARS-CoV-2 pandemic were proposed in the past. Unknown parameters of these models are often estimated based on observational data. However, lag in case-reporting, changing … testing policy or incompleteness of data lead to biased estimates. Moreover, parametrization is time-dependent due to changing age-structures, emerging virus variants, non-pharmaceutical interventions, and vaccination programs. To cover these aspects, we propose a principled approach to parametrize a SIR-type epidemiologic model by embedding it as a hidden layer into an input-output non-linear dynamical system (IO-NLDS). Observable data are coupled to hidden states of the model by appropriate data models considering possible biases of the data. This includes data issues such as known delays or biases in reporting. We estimate model parameters including their time-dependence by a Bayesian knowledge synthesis process considering parameter ranges derived from external studies as prior information. We applied this approach on a specific SIR-type model and data of Germany and Saxony demonstrating good prediction performances. Our approach can estimate and compare the relative effectiveness of non-pharmaceutical interventions and provide scenarios of the future course of the epidemic under specified conditions. It can be translated to other data sets, i.e., other countries and other SIR-type models.

Authors: Y. Kheifetz, H. Kirsten, M. Scholz

Date Published: 2nd Jul 2022

Publication Type: Journal article

Human Diseases: COVID-19

Ontological modelling and execution of phenotypic queries in the Leipzig Health Atlas
SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

Sharing data is of great importance for research in medical sciences. It is the basis for reproducibility and reuse of already generated outcomes in new projects and in new contexts. FAIR data principles … are the basics for sharing data. The Leipzig Health Atlas (LHA) platform follows these principles and provides data, describing metadata, and models that have been implemented in novel software tools and are available as demonstrators. LHA reuses and extends three different major components that have been previously developed by other projects. The SEEK management platform is the foundation providing a repository for archiving, presenting and secure sharing a wide range of publication results, such as published reports, (bio)medical data as well as interactive models and tools. The LHA Data Portal manages study metadata and data allowing to search for data of interest. Finally, PhenoMan is an ontological framework for phenotype modelling. This paper describes the interrelation of these three components. In particular, we use the PhenoMan to, firstly, model and represent phenotypes within the LHA platform. Then, secondly, the ontological phenotype representation can be used to generate search queries that are executed by the LHA Data Portal. The PhenoMan generates the queries in a novel domain specific query language (SDQL), which is specific for data management systems based on CDISC ODM standard, such as the LHA Data Portal. Our approach was successfully applied to represent phenotypes in the Leipzig Health Atlas with the possibility to execute corresponding queries within the LHA Data Portal.

Authors: Alexandr Uciteli, Christoph Beger, Jonas Wagner, Alexander Kiel, Frank A Meineke, Sebastian Stäubert, Matthias Löbe, René Hänsel, Judith Schuster, Toralf Kirsten, Heinrich Herre

Date Published: 1st May 2021

Publication Type: InCollection

Ontological Modelling and Execution of Phenotypic Queries in the Leipzig Health Atlas.
LHA - Leipzig Health Atlas, Onto-Med Research Group, SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

Sharing data is of great importance for research in medical sciences. It is the basis for reproducibility and reuse of already generated outcomes in new projects and in new contexts. FAIR data principles … are the basics for sharing data. The Leipzig Health Atlas (LHA) platform follows these principles and provides data, describing metadata, and models that have been implemented in novel software tools and are available as demonstrators. LHA reuses and extends three different major components that have been previously developed by other projects. The SEEK management platform is the foundation providing a repository for archiving, presenting and secure sharing a wide range of publication results, such as published reports, (bio)medical data as well as interactive models and tools. The LHA Data Portal manages study metadata and data allowing to search for data of interest. Finally, PhenoMan is an ontological framework for phenotype modelling. This paper describes the interrelation of these three components. In particular, we use the PhenoMan to, firstly, model and represent phenotypes within the LHA platform. Then, secondly, the ontological phenotype representation can be used to generate search queries that are executed by the LHA Data Portal. The PhenoMan generates the queries in a novel domain specific query language (SDQL), which is specific for data management systems based on CDISC ODM standard, such as the LHA Data Portal. Our approach was successfully applied to represent phenotypes in the Leipzig Health Atlas with the possibility to execute corresponding queries within the LHA Data Portal.

Authors: A. Uciteli, C. Beger, J. Wagner, A. Kiel, F. A. Meineke, S. Staubert, M. Lobe, R. Hansel, J. Schuster, T. Kirsten, H. Herre

Date Published: 24th May 2021

Publication Type: Journal article

Ontological modelling and FHIR Search based representation of basic eligibility criteria
LHA - Leipzig Health Atlas, Onto-Med Research Group, SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

Planning clinical studies to check medical hypotheses requires the specification of eligibility criteria in order to identify potential study participants. Electronically available patient data allows … to support the recruitment of patients for studies. The Smart Medical Information Technology for Healthcare (SMITH) consortium aims to establish data integration centres to enable the innovative use of available healthcare data for research and treatment optimization. The data from the electronic health record of patients in the participating hospitals is integrated into a Health Data Storage based on the Fast Healthcare Interoperability Resources standard (FHIR), developed by HL7. In SMITH, FHIR Search is used to query the integrated data. An investigation has shown the advantages and disadvantages of using FHIR Search for specifying eligibility criteria. This paper presents an approach for modelling eligibility criteria as well as for generating and executing FHIR Search queries. Our solution is based on the Phenotype Manager, a general ontological phenotyping framework to model and calculate phenotypes using the Core Ontology of Phenotypes.

Authors: A. Uciteli, C. Beger, J. Wagner, T. Kirsten, F. A. Meineke, S. Staubert, M. Lobe, H. Herre

Date Published: 26th Apr 2021

Publication Type: Journal article

Ontological Modelling and Reasoning of Phenotypes
LHA - Leipzig Health Atlas, Onto-Med Research Group, SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

The successful determination and analysis of phenotypes plays a key role in the diagnostic process, the evaluation of risk factors and the recruitment of participants for clinical and epidemiological … studies. The development of computable phenotype algorithms to solve these tasks is a challenging problem, caused by various reasons. Firstly, the term ‘phenotype’ has no generally agreed definition and its meaning depends on context. Secondly, the phenotypes are most commonly specified as non-computable descriptive documents. Recent attempts have shown that ontologies are a suitable way to handle phenotypes and that they can support clinical research and decision making. The SMITH Consortium is dedicated to rapidly establish an integrative medical informatics framework to provide physicians with the best available data and knowledge and enable innovative use of healthcare data for research and treatment optimization. In the context of a methodological use case “phenotype pipeline” (PheP), a technology to automatically generate phenotype classifications and annotations based on electronic health records (EHR) is developed. A large series of phenotype algorithms will be implemented. This implies that for each algorithm a classification scheme and its input variables have to be defined. Furthermore, a phenotype engine is required to evaluate and execute developed algorithms. In this article we present a Core Ontology of Phenotypes (COP) and a software Phenotype Manager (PhenoMan), which implements a novel ontology-based method to model and calculate phenotypes. Our solution includes an enhanced iterative reasoning process combining classification tasks with mathematical calculations at runtime. The ontology as well as the reasoning method were successfully evaluated based on different phenotypes (including SOFA score, socioeconomic status, body surface area and WHO BMI classification) and several data sets.

Authors: Alexandr Uciteli, Christoph Beger, Toralf Kirsten, Frank A. Meineke, Heinrich Herre

Date Published: 20th Dec 2019

Publication Type: InProceedings

Ontological representation, classification and data-driven computing of phenotypes
SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

BACKGROUND: The successful determination and analysis of phenotypes plays a key role in the diagnostic process, the evaluation of risk factors and the recruitment of participants for clinical and … epidemiological studies. The development of computable phenotype algorithms to solve these tasks is a challenging problem, caused by various reasons. Firstly, the term ’phenotype’ has no generally agreed definition and its meaning depends on context. Secondly, the phenotypes are most commonly specified as non-computable descriptive documents. Recent attempts have shown that ontologies are a suitable way to handle phenotypes and that they can support clinical research and decision making. The SMITH Consortium is dedicated to rapidly establish an integrative medical informatics framework to provide physicians with the best available data and knowledge and enable innovative use of healthcare data for research and treatment optimisation. In the context of a methodological use case ’phenotype pipeline’ (PheP), a technology to automatically generate phenotype classifications and annotations based on electronic health records (EHR) is developed. A large series of phenotype algorithms will be implemented. This implies that for each algorithm a classification scheme and its input variables have to be defined. Furthermore, a phenotype engine is required to evaluate and execute developed algorithms. RESULTS: In this article, we present a Core Ontology of Phenotypes (COP) and the software Phenotype Manager (PhenoMan), which implements a novel ontology-based method to model, classify and compute phenotypes from already available data. Our solution includes an enhanced iterative reasoning process combining classification tasks with mathematical calculations at runtime. The ontology as well as the reasoning method were successfully evaluated with selected phenotypes including SOFA score, socio-economic status, body surface area and WHO BMI classification based on available medical data. CONCLUSIONS: We developed a novel ontology-based method to model phenotypes of living beings with the aim of automated phenotype reasoning based on available data. This new approach can be used in clinical context, e.g., for supporting the diagnostic process, evaluating risk factors, and recruiting appropriate participants for clinical and epidemiological studies.

Authors: Alexandr Uciteli, Christoph Beger, Toralf Kirsten, Frank A Meineke, Heinrich Herre

Date Published: 1st Dec 2020

Publication Type: Journal article

Ontological representation, classification and data-driven computing of phenotypes.
LHA - Leipzig Health Atlas, Onto-Med Research Group, SMITH - Smart Medical Information Technology for Healthcare

Abstract (Expand)

BACKGROUND: The successful determination and analysis of phenotypes plays a key role in the diagnostic process, the evaluation of risk factors and the recruitment of participants for clinical and … epidemiological studies. The development of computable phenotype algorithms to solve these tasks is a challenging problem, caused by various reasons. Firstly, the term 'phenotype' has no generally agreed definition and its meaning depends on context. Secondly, the phenotypes are most commonly specified as non-computable descriptive documents. Recent attempts have shown that ontologies are a suitable way to handle phenotypes and that they can support clinical research and decision making. The SMITH Consortium is dedicated to rapidly establish an integrative medical informatics framework to provide physicians with the best available data and knowledge and enable innovative use of healthcare data for research and treatment optimisation. In the context of a methodological use case 'phenotype pipeline' (PheP), a technology to automatically generate phenotype classifications and annotations based on electronic health records (EHR) is developed. A large series of phenotype algorithms will be implemented. This implies that for each algorithm a classification scheme and its input variables have to be defined. Furthermore, a phenotype engine is required to evaluate and execute developed algorithms. RESULTS: In this article, we present a Core Ontology of Phenotypes (COP) and the software Phenotype Manager (PhenoMan), which implements a novel ontology-based method to model, classify and compute phenotypes from already available data. Our solution includes an enhanced iterative reasoning process combining classification tasks with mathematical calculations at runtime. The ontology as well as the reasoning method were successfully evaluated with selected phenotypes including SOFA score, socio-economic status, body surface area and WHO BMI classification based on available medical data. CONCLUSIONS: We developed a novel ontology-based method to model phenotypes of living beings with the aim of automated phenotype reasoning based on available data. This new approach can be used in clinical context, e.g., for supporting the diagnostic process, evaluating risk factors, and recruiting appropriate participants for clinical and epidemiological studies.

Authors: A. Uciteli, C. Beger, T. Kirsten, F. A. Meineke, H. Herre

Date Published: 21st Dec 2020

Publication Type: Journal article

Ontology-Based Assessment of Functional Redundancy in Health Information Systems
Management of health information systems

Abstract

Not specified

Authors: Alfred Winter, Alexander Strübing, Birgit Brigl, Reinhold Haux, Lutz Ißler

Date Published: 2009

Publication Type: Journal article

Ontology-Based Modelling of Web Content: Example Leipzig Health Atlas
Onto-Med Research Group

Abstract (Expand)

The realisation of a complex web portal, including the modelling of content, is a challenging process. The contents describe different interconnected entities that form a complex structure. The entities … and their relations have to be systematically analysed, and the content has to be specified and integrated into a content management system (CMS). Ontologies provide a suitable solution for modelling and specifying complex entities and their relations. However, the functionality for automated import of ontologies is not available in current content management systems. In order to describe the content of a web portal, we developed an ontology. Based on this ontology, we implemented a pipeline that allows the specification of the portal’s content and its import into the CMS Drupal. Our method is generic. It enables the development of web portals with the focus on a suitable representation of structured knowledge (entities, their properties and relations). Furthermore, it makes it possible to represent existing ontologies in such a way that their content can be understood by users without knowledge of ontologies and their semantics. Our approach has successfully been applied in building the LHA (Leipzig Health Atlas) portal, which provides access to metadata, data, publications and methods from various research projects at the University of Leipzig.

Authors: A. Uciteli, C. Beger, C. Rillich, F. A. Meineke, M. Loffler, H. Herre

Date Published: 2018

Publication Type: InBook

Ontology-based Retrieval of Scientific Data in LIFE
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

LIFE is an epidemiological study determining thousands of Leipzig inhabitants with a wide spectrum of interviews, questionnaires, and medical investigations. The heterogeneous data are centrally … integrated into a research database and are analyzed by specific analysis projects. To semantically describe the large set of data, we have developed an ontological framework. Applicants of analysis projects and other interested people can use the LIFE Investigation Ontology (LIO) as central part of the framework to get insights, which kind of data is collected in LIFE. Moreover, we use the framework to generate queries over the collected scientific data in order to retrieve data as requested by each analysis project. A query generator transforms the ontological specifications using LIO to database queries which are implemented as project-specific database views. Since the requested data is typically complex, a manual query specification would be very timeconsuming, error-prone, and is, therefore, unsuitable in this large project. We present the approach, overview LIO and show query formulation and transformation. Our approach runs in production mode for two years in LIFE.

Authors: Toralf Kirsten, A. Uciteli

Date Published: 2015

Publication Type: Not specified

Open and linkable Knowledge about Management of Health Information Systems
Management of health information systems

Abstract

Not specified

Authors: Konrad Höffner, Franziska Jahn, Anna Lörke, Thomas Pause, Birgit Schneider, Elske Ammenwerth, Alfred Winter

Date Published: 2019

Publication Type: InCollection

oposSOM-Browser: an interactive tool to explore omics data landscapes in health science
LHA - Leipzig Health Atlas, oBIG - omics Bioinformatics for Health

Abstract (Expand)

Background: oposSOM is a comprehensive, machine learning based open-source data analysis software combining functionalities such as diversity analyses, biomarker selection, function mining, and … visualization. Results: These functionalities are now available as interactive web-browser application for a broader user audience interested in extracting detailed information from high-throughput omics data sets pre-processed by oposSOM. It enables interactive browsing of single-gene and gene set profiles, of molecular 'portrait landscapes', of associated phenotype diversity, and signalling pathway activation patterns. Conclusion: The oposSOM-Browser makes available interactive data browsing for five transcriptome data sets of cancer (melanomas, B-cell lymphomas, gliomas) and of peripheral blood (sepsis and healthy individuals) at www.izbi.uni-leipzig.de/opossom-browser .

Authors: Henry Loeffler-Wirth, Jasmin Reikowski, Siras Hakobyan, Jonas Wagner, Hans Binder

Date Published: 1st Dec 2020

Publication Type: Journal article

oposSOM: R-package for high-dimensional portraying of genome-wide expression landscapes on bioconductor.
HNPCC-Sys - Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome

Abstract (Expand)

MOTIVATION: Comprehensive analysis of genome-wide molecular data challenges bioinformatics methodology in terms of intuitive visualization with single-sample resolution, biomarker selection, functional … information mining and highly granular stratification of sample classes. oposSOM combines those functionalities making use of a comprehensive analysis and visualization strategy based on self-organizing maps (SOM) machine learning which we call 'high-dimensional data portraying'. The method was successfully applied in a series of studies using mostly transcriptome data but also data of other OMICs realms. AVAILABILITY AND IMPLEMENTATION: oposSOM is now publicly available as Bioconductor R package. CONTACT: wirth@izbi.uni-leipzig.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Authors: H. Loffler-Wirth, M. Kalcher, H. Binder

Date Published: 1st Oct 2015

Publication Type: Not specified

OP-Register und Arztbriefschreibung mit MDVS
Management of health information systems

Abstract

Not specified

Authors: R. Sawinski, J. Hampl, R. Werner, J. Winkler, Alfred Winter, Reinhold Haux, St. Kunze

Date Published: 1993

Publication Type: Journal article

Optimism and pessimism in the general population: Psychometric properties of the Life Orientation Test (LOT-R)
LIFE Adult

Abstract (Expand)

Background/Objective: The Life Orientation Test-Revised (LOT-R) is often used to assess dispositional optimism. The aims of this study were to test psychometric properties of the LOT-R, to provide … normative scores, and to test the association between optimism and several psychological, sociodemographic, and behavioral factors. Method: A randomly selected German general population community sample with an age range of 18-80 years (N = 9,711) was surveyed. Results: The Confirmatory Factor Analysis (CFA) proved two (correlated) factors: Optimism and Pessimism. Invariance tests across gender and age groups confirmed metric invariance. There were only small gender differences in the LOT-R total score (M = 16.4 for females and M = 16.1 for males). The correlation between the subscales Optimism and Pessimism was strong for young and well educated people. Low optimism mean scores were observed for unemployed people, people with low income, smokers, and obese people. Normative scores of the LOT-R are provided. Conclusions: The study confirmed the bidimensional structure of the LOT-R and invariance across age and gender. We can recommend using this instrument for measuring dispositional optimism and pessimism in epidemiological research and clinical practice.

Authors: A. Hinz, C. Sander, H. Glaesmer, E. Brähler, M. Zenger, A. Hilbert, R. D. Kocalevent

Date Published: 1st May 2017

Publication Type: Journal article

Optimization-Based Speckle Tracking Algorithm for Left Ventricle Strain Estimation: A Feasibility Study.
LIFE Adult

Abstract (Expand)

Speckle tracking echocardiography (STE) is a widespread method for calculating myocardial strains and estimating left ventricle function. Since echocardiographic clips are corrupted by speckle decorrelation … noise, resulting in irregular, nonphysiological tissue displacement fields, smoothing is performed on the displacement data, affecting the strain results. Thus, strain results may depend on the specific implementations of 2-D STE, as well as other systems' characteristics of the various vendors. A novel algorithm (called K-SAD) is introduced, which integrates the physiological constraint of smoothness of the displacement field into an optimization process. Simulated B-mode clips, modeling healthy and abnormal cases, were processed by K-SAD. Peak global and subendocardial longitudinal strains, as well as regional strains, were calculated. In addition, 410 healthy subjects were also processed. The results of K-SAD are compared with those of one of the leading commercial product. K-SAD provides global mid-wall strain values, as well as subendocardial and regional strain values, all in good agreement with the ground-truth-simulated phantom data. K-SAD peak global longitudinal systolic strain values for 410 healthy subjects are quite similar for the different regions: - 17.02 +/- 4.02%, - 19.00 +/- 3.45%, and - 19.72 +/- 5.06% at the basal, mid, and apical regions, respectively. Improved performance under noisy conditions was demonstrated by comparing a subgroup of 40 subjects with the best image quality with the remaining 370 cohort: K-SAD provides statistically similar global and regional results for the two cohorts. Our study indicates that the sensitivity of strain values to speckle noise, caused by the post block-matching weighted smoothing, can be significantly reduced and accuracy enhanced by employing an integrated one-stage, physiologically constrained optimization process.

Authors: H. Khamis, S. Shimoni, A. Hagendorff, N. Smirin, Z. Friedman, D. Adam

Date Published: 24th May 2016

Publication Type: Journal article

Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: In the SMARTE-R-CHOP-14 … trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6xR-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6xR-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. RESULTS: The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. CONCLUSION: Extended rituximab exposure compared with eight 2-week applications in combination with 6xR-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6xR-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.

Authors: M. Pfreundschuh, V. Poeschel, S. Zeynalova, M. Hanel, G. Held, N. Schmitz, A. Viardot, M. H. Dreyling, M. Hallek, C. Mueller, M. H. Wiesen, M. Witzens-Harig, L. Truemper, U. Keller, T. Rixecker, C. Zwick, N. Murawski

Date Published: 20th Dec 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSE-R-CHOP-14 trial of the DSHNHL.
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial. PATIENTS AND METHODS: Rituximab (375 … mg/m(2)) was given on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60. RESULTS: One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3-5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0). CONCLUSIONS: Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.

Authors: N. Murawski, M. Pfreundschuh, S. Zeynalova, V. Poeschel, M. Hanel, G. Held, N. Schmitz, A. Viardot, C. Schmidt, M. Hallek, M. Witzens-Harig, L. Trumper, T. Rixecker, C. Zwick

Date Published: 15th Jun 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients.
GLA - German Lymphoma Alliance

Abstract (Expand)

Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B-cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male DLBCL … patients. Elderly patients (61-80 years) received 6 cycles CHOP-14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14-day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m(2) , females 375 mg/m(2) ) every 2 weeks or according to an upfront dose-dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose-dense rituximab schedule was found (3-year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m(2) dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression-free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m(2) was not more toxic than 375 mg/m(2) rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex-specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.

Authors: M. Pfreundschuh, N. Murawski, S. Zeynalova, M. Ziepert, M. Loeffler, M. Hanel, J. Dierlamm, U. Keller, M. Dreyling, L. Truemper, N. Frickhofen, A. N. Hunerliturkoglu, N. Schmitz, V. Poschel, T. Rixecker, C. Berdel, C. Rube, G. Held, C. Zwick

Date Published: 11th Oct 2017

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Outcome of elderly patients with diffuse large B-cell lymphoma treated with R-CHOP: results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

Background: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK … NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients >/=60 years treated on the R-CHOP14v21 trial with extended follow-up. Patients and methods: Six hundred and four R-CHOP14v21 patients >/=60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. Results: Elderly DLBCL patients received high dose intensities with median total doses of >/=98% for all agents. Toxicities were similar in both arms with the exception of more grade >/=3 neutropenia (P < 0.0001) and fewer grade >/=3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. Conclusions: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. Trial numbers: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).

Authors: A. Kuhnl, D. Cunningham, N. Counsell, E. A. Hawkes, W. Qian, P. Smith, N. Chadwick, A. Lawrie, P. Mouncey, A. Jack, C. Pocock, K. M. Ardeshna, J. Radford, A. McMillan, J. Davies, D. Turner, A. Kruger, P. W. Johnson, J. Gambell, A. Rosenwald, G. Ott, H. Horn, M. Ziepert, M. Pfreundschuh, D. Linch

Date Published: 1st Jul 2017

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Outcomes of stable and unstable patterns of subjective cognitive decline - results from the Leipzig Longitudinal Study of the Aged (LEILA75+).
LIFE Adult

Abstract (Expand)

BACKGROUND: Subjective cognitive decline (SCD), i.e., the self-perceived feeling of worsening cognitive function, may be the first notable syndrome of preclinical Alzheimer's disease and other … dementias. However, not all individuals with SCD progress. Stability of SCD, i.e., repeated reports of SCD, could contribute to identify individuals at risk, as stable SCD may more likely reflect the continuous neurodegenerative process of Alzheimer's and other dementias. METHODS: Cox regression analyses were used to assess the association between stability of SCD and progression to MCI and dementia in data derived from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). RESULTS: Of 453 cognitively unimpaired individuals with a mean age of 80.5 years (SD = 4.2), 139 (30.7 %) reported SCD at baseline. Over the study period (M = 4.8 years, SD = 2.2), 84 (18.5 %) individuals had stable SCD, 195 (43.1 %) unstable SCD and 174 (38.4 %) never reported SCD. Stable SCD was associated with increased risk of progression to MCI and dementia (unadjusted HR = 1.8, 95 % CI = 1.2-2.6; p < .01), whereas unstable SCD yielded a decreased progression risk (unadjusted HR = 0.5, 95 % CI = 0.4-0.7; p < .001) compared to no SCD. When adjusted for baseline cognitive functioning, progression risk in individuals with stable SCD was significantly increased in comparison to individuals with unstable SCD, but not compared to individuals without SCD. CONCLUSIONS: Our results, though preliminary, suggest that stable SCD, i.e., repeated reports of SCD, may yield an increased risk of progression to MCI and dementia compared to unstable SCD. Baseline cognitive scores, though within a normal range, seem to be a driver of progression in stable SCD. Future research is warranted to investigate whether stability could hold as a SCD research feature.

Authors: S. Roehr, A. Villringer, M. C. Angermeyer, T. Luck, S. G. Riedel-Heller

Date Published: 4th Nov 2016

Publication Type: Journal article

Human Diseases: dementia, Alzheimer's disease

Ovarian and breast cancer risks associated with pathogenic variants in RAD51C and RAD51D
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

BACKGROUND The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. METHODS We … We analysed data from 6178 families, 125 with pathogenic variants in RAD51C; and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families, while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. RESULTS Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C RR = 7.55, 95%CI:5.60-10.19, p = 5 \times 10-40; RAD51D RR = 7.60, 95%CI:5.61-10.30, p = 5 \times 10-39) and BC (RAD51C RR = 1.99, 95%CI:1.39-2.85, p = 1.55 \times 10-4; RAD51D RR = 1.83, 95%CI:1.24-2.72, p = 0.002). For both RAD51C and RAD51D, there was a suggestion that the TOC RRs increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 were 11% (95%CI:6-21%) for RAD51C and 13% (95%CI:7-23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 were 21% (95%CI:15-29%) for RAD51C and 20% (95%CI:14-28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C/D pathogenic variant carriers varied by cancer family history, and could be as high as 32-36% for TOC, for carriers with two first degree relatives diagnosed with TOC; or 44-46% for BC, for carriers with two first degree relatives diagnosed with BC. CONCLUSIONS These estimates will facilitate the genetic counselling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models.

Authors: Xin Yang, Honglin Song, Goska Leslie, Christoph Engel, Eric Hahnen, Bernd Auber, Judit Horváth, Karin Kast, Dieter Niederacher, Clare Turnbull, Richard Houlston, Helen Hanson, Chey Loveday, Jill S. Dolinsky, Holly Laduca, Susan J. Ramus, Usha Menon, Adam N. Rosenthal, Ian Jacobs, Simon A. Gayther, Ed Dicks, Heli Nevanlinna, Kristiina Aittomäki, Liisa M. Pelttari, Hans Ehrencrona, Åke Borg, Anders Kvist, Barbara Rivera, Thomas v. O. Hansen, Malene Djursby, Andrew Lee, Joe Dennis, David D. Bowtell, Nadia Traficante, Orland Diez, Judith Balmaña, Stephen B. Gruber, Georgia Chenevix-Trench, Allan Jensen, Susanne K. Kjær, Estrid Høgdall, Laurent Castéra, Judy Garber, Ramunas Janavicius, Ana Osorio, Lisa Golmard, Ana Vega, Fergus J. Couch, Mark Robson, Jacek Gronwald, Susan M. Domchek, Julie O. Culver, Miguel de La Hoya, Douglas F. Easton, William D. Foulkes, Marc Tischkowitz, Alfons Meindl, Rita K. Schmutzler, Paul D. P. Pharoah, Antonis C. Antoniou

Date Published: 28th Feb 2020

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian … cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 \times 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 \times 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 \times 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

Authors: Susan J. Ramus, Antonis C. Antoniou, Karoline B. Kuchenbaecker, Penny Soucy, Jonathan Beesley, Xiaoqing Chen, Lesley McGuffog, Olga M. Sinilnikova, Sue Healey, Daniel Barrowdale, Andrew Lee, Mads Thomassen, Anne-Marie Gerdes, Torben A. Kruse, Uffe Birk Jensen, Anne-Bine Skytte, Maria A. Caligo, Annelie Liljegren, Annika Lindblom, Håkan Olsson, Ulf Kristoffersson, Marie Stenmark-Askmalm, Beatrice Melin, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska, Katarzyna Durda, Elżbieta Złowocka, Jacek Gronwald, Tomasz Huzarski, Tomasz Byrski, Cezary Cybulski, Aleksandra Toloczko-Grabarek, Ana Osorio, Javier Benitez, Mercedes Duran, Maria-Isabel Tejada, Ute Hamann, Matti Rookus, Flora E. van Leeuwen, Cora M. Aalfs, Hanne E. J. Meijers-Heijboer, Christi J. van Asperen, K. E. P. van Roozendaal, Nicoline Hoogerbrugge, J. Margriet Collée, Mieke Kriege, Rob B. van der Luijt, Susan Peock, Debra Frost, Steve D. Ellis, Radka Platte, Elena Fineberg, D. Gareth Evans, Fiona Lalloo, Chris Jacobs, Ros Eeles, Julian Adlard, Rosemarie Davidson, Diana Eccles, Trevor Cole, Jackie Cook, Joan Paterson, Fiona Douglas, Carole Brewer, Shirley Hodgson, Patrick J. Morrison, Lisa Walker, Mary E. Porteous, M. John Kennedy, Harsh Pathak, Andrew K. Godwin, Dominique Stoppa-Lyonnet, Virginie Caux-Moncoutier, Antoine de Pauw, Marion Gauthier-Villars, Sylvie Mazoyer, Mélanie Léoné, Alain Calender, Christine Lasset, Valérie Bonadona, Agnès Hardouin, Pascaline Berthet, Yves-Jean Bignon, Nancy Uhrhammer, Laurence Faivre, Catherine Loustalot, Saundra Buys, Mary Daly, Alex Miron, Mary Beth Terry, Wendy K. Chung, Esther M. John, Melissa Southey, David Goldgar, Christian F. Singer, Muy-Kheng Tea, Georg Pfeiler, Anneliese Fink-Retter, Thomas v. O. Hansen, Bent Ejlertsen, Oskar Th Johannsson, Kenneth Offit, Tomas Kirchhoff, Mia M. Gaudet, Joseph Vijai, Mark Robson, Marion Piedmonte, Kelly-Anne Phillips, Linda van Le, James S. Hoffman, Amanda Ewart Toland, Marco Montagna, Silvia Tognazzo, Evgeny Imyanitov, Claudine Issacs, Ramunas Janavicius, Conxi Lazaro, Iganacio Blanco, Eva Tornero, Matilde Navarro, Kirsten B. Moysich, Beth Y. Karlan, Jenny Gross, Edith Olah, Tibor Vaszko, Soo-Hwang Teo, Patricia A. Ganz, Mary S. Beattie, Cecelia M. Dorfling, Elizabeth J. van Rensburg, Orland Diez, Ava Kwong, Rita K. Schmutzler, Barbara Wappenschmidt, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Simone Heidemann, Dieter Niederacher, Sabine Preisler-Adams, Dorotehea Gadzicki, Raymonda Varon-Mateeva, Helmut Deissler, Andrea Gehrig, Christian Sutter, Karin Kast, Britta Fiebig, Dieter Schäfer, Trinidad Caldes, Miguel de La Hoya, Heli Nevanlinna, Kristiina Aittomäki, Marie Plante, Amanda B. Spurdle, Susan L. Neuhausen, Yuan Chun Ding, Xianshu Wang, Noralane Lindor, Zachary Fredericksen, V. Shane Pankratz, Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Bernardo Bonanni, Loris Bernard, Riccardo Dolcetti, Laura Papi, Laura Ottini, Paolo Radice, Mark H. Greene, Phuong L. Mai, Irene L. Andrulis, Gord Glendon, Hilmi Ozcelik, Paul D. P. Pharoah, Simon A. Gayther, Jacques Simard, Douglas F. Easton, Fergus J. Couch, Georgia Chenevix-Trench

Date Published: 1st Apr 2012

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

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