Circulating Oxytocin Is Genetically Determined and Associated with Obesity and Impaired Glucose Tolerance

Abstract

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 ± SD, 47.7 ± 15.2 years) with subphenotypes related to obesity, including anthropometric traits such as body mass index [BMI (mean ± SD), 26.8 ± 4.6 kg/m2], waist-to-hip ratio (WHR; 0.88 ± 0.09), blood parameters (glucose, 5.32 ± 0.50 mmol/L; insulin, 5.3 ± 3.3 μU/mL), and oral glucose tolerance test to clarify the association with OXT. We also tested in a genome-wide association study (GWAS) whether the interindividual 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 <25 kg/m2 was significantly lower (n = 256; 78.6 pg/mL) than in subjects with a BMI between 25 and 30 kg/m2 (n = 314; 98.5 pg/mL, P = 6 × 10-6) and with BMI >30 kg/m2 (n = 137; 106.4 pg/mL, P = 8 × 10-6). OXT levels were also positively correlated with plasma glucose and insulin and were elevated in subjects with impaired glucose tolerance (P = 4.6 × 10-3). Heritability of OXT was estimated at 12.8%. In a GWAS, two hits in linkage disequilibrium close (19 kb) to the OXT reached genome-wide significant association (top-hit rs12625893, P = 3.1 × 10-8, explained variance 3%). Conclusions: Our data show that OXT is genetically affected by a variant near OXT and is associated with obesity and impaired glucose tolerance.