Genetic correlations of psychiatric traits with body composition and glycemic traits are sex- and age-dependent

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  • Christopher Hübel, King's College London, South London and Maudsley NHS Foundation Trust, Karolinska Institutet
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  • Héléna A. Gaspar, King's College London, South London and Maudsley NHS Foundation Trust
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  • Jonathan R.I. Coleman, King's College London, South London and Maudsley NHS Foundation Trust
  • ,
  • Ken B. Hanscombe, King's College London
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  • Kirstin Purves, King's College London
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  • Inga Prokopenko, University of Surrey, UK
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  • Mariaelisa Graff, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Julius S. Ngwa, Johns Hopkins University, Boston University School of Public Health
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  • Tsegaselassie Workalemahu, National Institutes of Health
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  • Paul F. O’Reilly, King's College London
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  • Cynthia M. Bulik, Karolinska Institutet, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Gerome Breen, King's College London, South London and Maudsley NHS Foundation Trust
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  • ADHD Working Group of the Psychiatric Genomics Consortium
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  • Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC)
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  • Autism Working Group of the Psychiatric Genomics Consortium
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  • Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
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  • Eating Disorders Working Group of the Psychiatric Genomics Consortium
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  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
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  • OCD & Tourette Syndrome Working Group of the Psychiatric Genomics Consortium
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  • PTSD Working Group of the Psychiatric Genomics Consortium
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  • Schizophrenia Working Group of the Psychiatric Genomics Consortium
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  • Sex Differences Cross Disorder Working Group of the Psychiatric Genomics Consortium
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  • Substance Use Disorders Working Group of the Psychiatric Genomics Consortium
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  • German Borderline Genomics Consortium
  • ,
  • International Headache Genetics Consortium

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.

Original languageEnglish
Article number5765
JournalNature Communications
Volume10
Issue1
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - 2019

    Research areas

  • ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, BIOLOGICAL INSIGHTS, EATING-DISORDERS, GENOME-WIDE ASSOCIATION, MASS INDEX, METAANALYSIS, OBESITY, POOLED ANALYSIS, RISK-FACTORS, SUSCEPTIBILITY LOCI

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