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

Autor: Yilmaz Z; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Halvorsen M; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Bryois J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Yu D; Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Thornton LM; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zerwas S; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Micali N; Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; UCL Institute of Child Health, UCL, London, UK.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Moessner R; Department of Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany., Burton CL; Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada., Zai G; Neurogenetics Section, Molecular Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.; Department of Psychiatry, University of Toronto, Toronto, ON, Canada., Erdman L; Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada., Kas MJ; Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Arnold PD; Genetics & Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.; Mathison Centre for Mental Health Research & Education, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Davis LK; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA., Knowles JA; SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA., Breen G; MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK., Scharf JM; Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Nestadt G; Department of Psychiatry and Behavioral Science, Johns Hopkins University, Baltimore, MD, USA., Mathews CA; Department of Psychiatry, Genetics Institute, University of Florida, Gainesville, FL, USA., Bulik CM; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Mattheisen M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; The Lundbeck Foundation Initiative of Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.; Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Crowley JJ; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. crowley@unc.edu.; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. crowley@unc.edu.; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. crowley@unc.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2020 Sep; Vol. 25 (9), pp. 2036-2046. Date of Electronic Publication: 2018 Aug 07.
DOI: 10.1038/s41380-018-0115-4
Abstrakt: 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 (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., r g  = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., r g  = -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.
Databáze: MEDLINE