Preprint open access publication

Examination of the Shared Genetic Basis of Anorexia Nervosa and Obsessive-Compulsive Disorder

bioRxiv, Cold Spring Harbor Laboratory,

2017

DOI:10.1101/231076, Dimensions: pub.1099639984,

Affiliations

Organisations

  1. (1) University of North Carolina at Chapel Hill, grid.10698.36
  2. (2) Karolinska Institute, grid.4714.6
  3. (3) Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  4. (4) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  5. (5) University of Geneva, grid.8591.5
  6. (6) University of Tübingen, grid.10392.39
  7. (7) Hospital for Sick Children, grid.42327.30
  8. (8) Centre for Addiction and Mental Health, grid.155956.b
  9. (9) University of Toronto, grid.17063.33
  10. (10) Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, The Netherlands
  11. (11) University of Groningen, grid.4830.f
  12. (12) University of Calgary, grid.22072.35
  13. (13) Vanderbilt University Medical Center, grid.412807.8
  14. (14) University of Southern California, grid.42505.36
  15. (15) King's College London, grid.13097.3c
  16. (16) Johns Hopkins University, grid.21107.35
  17. (17) University of Florida, grid.15276.37
  18. (18) Aarhus University, grid.7048.b, AU

Description

ABSTRACT 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 crossdisorder GWAS meta-analysis of 3,495 AN cases, 2,688 OCD cases and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (r g = 0.49 ± 0.13, p = 9.07×10 −7 ) and a sizable SNP heritability (SNP h 2 = 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., bipolar disorder, schizophrenia, neuroticism) and negative correlations with metabolic phenotypes (e.g., BMI, 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.

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Times Cited: 1

Field Citation Ratio (FCR): 0.21

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Green, Published