Manuel Mattheisen

Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Zeynep Yilmaz, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Matthew Halvorsen, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Julien Bryois, Karolinska Institutet
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  • Dongmei Yu, Massachusetts General Hospital, Boston
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  • Laura M. Thornton, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Stephanie Zerwas, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States
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  • Nadia Micali, University of Geneva, UCL Institute of Child Health, London, UK., Icahn School of Medicine at Mount Sinai
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  • Rainald Moessner, University Tübingen
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  • Christie L. Burton, The Hospital for Sick Children
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  • Gwyneth Zai, Centre for Addiction and Mental Health, University of Toronto
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  • Lauren Erdman, The Hospital for Sick Children
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  • Martien J. Kas, Rijksuniversiteit Groningen, University Medical Center Utrecht, Utrecht
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  • Paul D. Arnold, The Hospital for Sick Children, University of Calgary
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  • Lea K. Davis, Vanderbilt University Medical Center, Department of Psychiatry and Behavioral Sciences
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  • James A. Knowles, SUNY Downstate Medical Center
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  • Gerome Breen, Medical Research Council Laboratories
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  • Jeremiah M. Scharf, Massachusetts General Hospital, Boston
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  • Gerald Nestadt, Johns Hopkins University Hospital
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  • Carol A. Mathews, University of Florida, Gainesville, Florida
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  • Cynthia M. Bulik, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States, Karolinska Institutet
  • ,
  • Manuel Mattheisen
  • James J. Crowley, The University of North Carolina at Chapel Hill, Department of Genetics, Chapel Hill, United States, Karolinska Institutet
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  • Eating Disorders Working Group of the Psychiatric Genomics Consortium, Tourette Syndrome/Obsessive–Compulsive Disorder Working Group of the Psychiatric Genomics Consortium

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = −0.25 with body mass index and −0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN–OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.

Original languageEnglish
JournalMolecular Psychiatry
Volume25
Issue9
Pages (from-to)2036-2046
ISSN1359-4184
DOIs
Publication statusPublished - Sep 2020

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