Abstract
Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emerge: (1) anorexia nervosa, schizophrenia, obsessive-compulsive disorder, and education years are negatively genetically correlated with body fat % and fat-free mass, whereas (2) attention-deficit/hyperactivity disorder (ADHD), alcohol dependence, insomnia, and heavy smoking are positively correlated. Anorexia nervosa shows a stronger genetic correlation with body fat % in females, whereas education years is more strongly correlated with fat mass in males. Education years and ADHD show genetic overlap with childhood obesity. Mendelian randomization identifies schizophrenia, anorexia nervosa, and higher education as causal for decreased fat mass, with higher body fat % possibly being a causal risk factor for ADHD and heavy smoking. These results suggest new possibilities for targeted preventive strategies.
Highlights
Body composition is often altered in psychiatric disorders
Body composition and physical activity showed substantial heritability explained by common genetic variation ranging from 28–51% (standard error (s.e.) = 0.4–0.8%, linkage disequilibrium score regression (LDSC); Supplementary Table 3) and sexdependent sets of genomic variation at pBonferroni = 0.05/28 = 0.002
Detailed results for the body composition and physical activity Genome-wide association studies (GWASs), including significant hits and Manhattan plots, are presented on Functional Mapping and Annotation (FUMA; URLs) entry 20–22 and 38–41
Summary
Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Several studies have shown negative genetic correlations of BMI with anorexia nervosa and schizophrenia[12,23,24,25] and positive genetic correlations of BMI with attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder[26,27] These observations suggest that an in-depth investigation of the shared genomics between psychiatric and body composition traits is needed. Both extreme overweight and extreme underweight show a clear sex difference: females are disproportionately affected by anorexia nervosa (with ratios up to 15:1) and by obesity (≥30 kg/m2)[28,29,30]. Hormones and sex chromosomes have clearly been demonstrated to play a role[35], but are insufficient to fully explain the sex differences[36]
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