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960 Publications visible to you, out of a total of 960
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Genetical Statistics and Systems Biology

Abstract (Expand)

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT … consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P \textless 5 \times 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Authors: Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. de Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Rujescu Dan, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, Ian J. Deary

Date Published: 1st Dec 2018

Publication Type: Journal article

Biomechanical properties of polymer-infiltrated ceramic crowns on one-piece zirconia implants after long-term chewing simulation
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Implant and superstructure provide a complex system, which has to withstand oral conditions. Concerning the brittleness of many ceramics, fractures are a greatly feared issue. Therefore, …, polymer-infiltrated ceramic networks (PICNs) were developed. Because of its low Young’s modulus and high elastic modulus, the PICN crown on a one-piece zirconia implant might absorb forces to prevent the system from fracturing in order to sustain oral forces. Recommendations for the material of superstructure on zirconia implants are lacking, and only one study investigates PICN crowns on these types of implants. Accordingly, this study aimed to examine PICN crowns on one-piece zirconia implants regarding bond strength and surface wear after long-term chewing simulation (CS). METHODS Twenty-five hybrid ceramic crowns (Vita Enamic, Vita Zahnfabrik) were produced using computer-aided design/computer-aided manufacturing (CAD/CAM) technology and adhesively bonded (RelyX™ Ultimate, 3M ESPE) to zirconia implants. Twenty of the specimens underwent simultaneous mechanical loading and thermocycling simulating a 5-year clinical situation (SD Mechatronik GmbH). Wear depth and wear volume, based on X-ray micro-computed tomography volume scans (Skyscan 1172-100-50, Bruker) before and after CS, were evaluated. All crowns were removed from the implants using a universal testing machine (Z010, Zwick GmbH&Co.KG). Subsequently, luting agent was light microscopically localized (Stemi 2000-C, Zeiss). With a scanning electron microscope (SEM, Phenom™ G2 pro, Phenom World), the area of abrasion was assessed. RESULTS 1. After CS, none of the tested crowns were fractured or loosened. 2. The maximum vertical wear after CS was M = 0.31 \pm 0.04 mm (mean \pm standard deviation), and the surface wear was M = 0.74 \pm 0.23 mm3. 3. The pull-off tests revealed a 1.8 times higher bond strength of the control group compared to the experimental group (t(23) = 8.69, p \textless 0.001). 4. Luting agent was mostly located in the crowns, not on the implants. 5. The area of abrasion showed avulsion and a rough surface. CONCLUSIONS PICN on one-piece zirconia implants showed high bond strength and high wear after CS.

Authors: Pia Baumgart, Holger Kirsten, Rainer Haak, Constanze Olms

Date Published: 1st Dec 2018

Publication Type: Journal article

Intra-individual alterations of serum markers routinely used in forensic pathology depending on increasing post-mortem interval
Genetical Statistics and Systems Biology

Abstract (Expand)

Post-mortem biochemistry of serum markers has been the subject of numerous studies, but in-situ marker stability after death has not been sufficiently evaluated yet. Such laboratory analyses are … especially necessary in the cases of functional deaths without morphological evidence of the death causes and also in cardiac death cases with only very short survival times. The aim of the study was to determine the post-mortem stability of commonly-used serum markers at predefined time points. In 20 cases, peripheral venous samples were taken starting immediately after circulatory arrest and ending 48 hours after death. Serum creatinine, urea, 3-\textgreekb-hydroxybutyrate, tryptase, myoglobin, troponin T, creatin kinase and creatin kinase-MB have been included. For all markers, we observed increasing marker levels for longer post-mortem intervals. Significant marker level changes began two hours after death. Excessive increases were observed for cardiac and muscle markers. Marker levels showed high intra-assay precision. Furthermore, the markers were robust enough to withstand freeze-thaw cycles. Potential contamination of arteriovenous blood did not influence the post-mortem marker levels. Post-mortem blood should be sampled as soon as possible, as increased post-mortem intervals may heavily change marker levels in-situ in individual cases, whereas the markers are mostly unaffected by laboratory conditions.

Authors: Lina Woydt, Michael Bernhard, Holger Kirsten, Ralph Burkhardt, Niels Hammer, André Gries, Jan Dreßler, Benjamin Ondruschka

Date Published: 1st Dec 2018

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

Commentary: Arguing for Adaptive Clinical Trials in Sepsis.
SMITH - Smart Medical Information Technology for Healthcare

Abstract

Not specified

Authors: M. Kesselmeier, A. Scherag

Date Published: 15th Nov 2018

Publication Type: Journal article

Parameters of pulse wave velocity: determinants and reference values assessed in the population-based study LIFE-Adult
Genetical Statistics and Systems Biology

Abstract (Expand)

AIMS AND BACKGROUND Parameters of arterial stiffness such as pulse wave velocity (PWV) were recently proposed as independent risk factors of cardiovascular events. We analyse three PWV parameters in …n the large population-based study LIFE-Adult to identify risk factors, normal and reference values. METHODS AND RESULTS Brachial-ankle (ba), brachial-femoral (bf) and carotid-femoral (cf) PWV assessment was performed using Vicorder device. 8509 participants aged 19-80 were analysed. PWV parameters were moderately correlated (r(ba/bf) = 0.6, r(ba/cf) = 0.46, r(bf/cf) = 0.59). Age and blood pressure are the dominant determinants of PWV parameters explaining \textgreater 18% of variability. Sex was only relevant for bfPWV and cfPWV. All further analysed cardiovascular and other risk factors are of minor importance. We provide age-dependent percentiles for the population (reference values) and for the subgroup of normotonic individuals. All percentiles show a strong increase with age. The difference between normotonic and all individuals is small for younger age groups but increases up to 1 m/s for elderly subjects. CONCLUSION Our study confirms and further underpins the strong impact of age and blood pressure on arterial stiffness and the relatively weak contribution of other factors, supporting an independent role of arterial stiffness in cardiovascular disease development. Age-dependent reference and normal values were provided on the basis of the so far largest study sample facilitating the implementation of PWV assessment in clinical practice. Due to better compliance, handling and stronger association with age and blood pressure, baPWV could serve as an alternative to cfPWV. Follow-up data are required to estimate the clinical significance of specified PWV cut-offs.

Authors: Daniel Baier, Andrej Teren, Kerstin Wirkner, Markus Loeffler, Markus Scholz

Date Published: 1st Nov 2018

Publication Type: Journal article

Commentary: Arguing for Adaptive Clinical Trials in Sepsis
SMITH - Smart Medical Information Technology for Healthcare

Abstract

Not specified

Authors: Miriam Kesselmeier, André Scherag

Date Published: 30th Oct 2018

Publication Type: Journal article

Human Diseases: disease by infectious agent

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