Circulating oxytocin is genetically determined and associated with obesity and impaired glucose tolerance

CONTEXT Despite the emerging evidence on the role of oxytocin (OXT) in metabolic diseases, there is a lack of well powered studies addressing the relationship of circulating OXT with obesity and diabetes. OBJECTIVES AND DESIGN Here, we measured OXT in a study cohort (n=721; 396 women, 325 men; mean age\pmSD - 47.7\pm15.2 years) with sub-phenotypes related to obesity including anthropometric traits such as body mass index (BMI; mean\pmSD - 47.7\pm15.2 kg/m2), waist-to-hip-ratio (WHR; 0.88\pm0.09), blood parameters (glucose - 5.32\pm0.50 mmol/l, insulin - 5.3\pm3.3 µU/ml, lipids) and oral glucose tolerance test (OGTT) to clarify the association with OXT. We also tested in a genome-wide association study (GWAS) whether the inter-individual variation in OXT serum levels might be explained by genetic variation. RESULTS The OXT concentration was increased in subjects with elevated BMI and positively correlated with WHR, waist circumference and triglyceride levels. The OXT concentration in subjects with BMI\textless25 kg/m2 was significantly lower (n=256; 78.6 pg/ml) than in subjects with a BMI between 25-30 kg/m2 (n=314; 98.5 pg/ml, p=6x10-6) and with BMI\textgreater30 kg/m2 (n=137; 106.4 pg/ml, p=8x10-6). OXT levels were also positively correlated with plasma glucose and insulin and were elevated in subjects with impaired glucose tolerance (p=4.6x10-3). Heritability of OXT was estimated to 12.8%. In a GWAS, two hits in linkage disequilibrium close (19kb) to the OXT reached genome-wide significant association (top-hit rs12625893, p=3.1x10-8, explained variance 3%). CONCLUSIONS Our data show that OXT is genetically affected by a variant in OXT and is associated with obesity and impaired glucose tolerance.