Anorexia nervosa (AN) is a mental illness with high mortality that most commonly afflicts adolescent female individuals. Clinical symptoms include chronic food refusal, weight loss and body image distortions. We carried out a genome-wide association study on 1033 AN cases and 3733 pediatric control subjects, all of whom were of European ancestry and were genotyped on the Illumina HumanHap610 platform (Illumina, San Diego, CA, USA). We confirmed that common single-nucleotide polymorphisms (SNPs) within OPRD1 (rs533123, P=0.0015) confer risk for AN, and obtained suggestive evidence that common SNPs near HTR1D (rs7532266, P=0.04) confer risk for restricting-type AN specifically. However, no SNPs reached genome-wide significance in our data, whereas top association signals were detected near ZNF804B, CSRP2BP, NTNG1, AKAP6 and CDH9. In parallel, we performed genome-wide analysis on copy number variations (CNVs) using the signal intensity data from the SNP arrays. We did not find evidence that AN cases have more CNVs than control subjects, nor do they have over-representation of rare or large CNVs. However, we identified several regions with rare CNVs that were only observed in AN cases, including a recurrent 13q12 deletion (1.5 Mb) disrupting SCAS in two cases, and CNVs disrupting the CNTN6/CNTN4 region in several AN cases. In conclusion, our study suggests that both common SNPs and rare CNVs may confer genetic risk to AN. These results point to intriguing genes that await further validation in independent cohorts for confirmatory roles in AN.
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Genetic investigation of the contribution of body composition to anorexia nervosa in an electronic health record setting
Translational Psychiatry Open Access 19 November 2022
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We gratefully thank all the patients and their families who were enrolled in this study, as well as all the control subjects who donated blood samples to Children's Hospital of Philadelphia (CHOP) for genetic research purposes. We thank the Price Foundation for their support of the Collaborative Group effort that was responsible for recruitment of patients, collection of clinical information and provision of the DNA samples used in this study. The authors also thank the Klarman Family Foundation for supporting the study. We thank the technical staff at the Center for Applied Genomics at CHOP for producing the genotypes used for analyses and the nursing, medical assistant and medical staff for their invaluable help with sample recruitments. CTB and NJS are funded in part by the Scripps Translational Sciences Institute Clinical Translational Science Award [Grant Number U54 RR0252204-01]. All genome-wide genotyping was funded by an Institute Development Award to the Center for Applied Genomics from the CHOP.
The authors declare no conflict of interest.
Supplementary Information accompanies the paper on the Molecular Psychiatry website
Members of the Price Foundation Collaborative Group
Harry Brandt7, Steve Crawford7, Scott Crow8, Manfred M Fichter9, Katherine A Halmi10, Craig Johnson11, Allan S Kaplan12,13,14, Maria La Via15, James Mitchell16,17, Michael Strober18, Alessandro Rotondo19, Janet Treasure20, D Blake Woodside13,14,21, Cynthia M Bulik15,22, Pamela Keel21, Kelly L Klump23, Lisa Lilenfeld24, Laura M Thornton15, Kathy Plotnicov25, Andrew W Bergen26 and Pierre Magistretti27
7Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
8Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA
9Roseneck Hospital for Behavioral Medicine, Prien, Germany and Department of Psychiatry, University of Munich (LMU), Munich, Germany
10New York Presbyterian Hospital-Westchester Division, Weill Medical College of Cornell, University, White Plains, NY, USA
11Eating Recovery Center, Denver, Colorado, USA
12Center for Addiction and Mental Health, Toronto, Canada
13Department of Psychiatry, Toronto General Hospital, University Health Network, Toronto, Canada
14Department of Psychiatry, University of Toronto, Toronto, Canada
15Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
16Neuropsychiatric Research Institute, Fargo, ND, USA
17Department of Clinical Neuroscience, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA
18Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
19Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnology, University of Pisa, Pisa, Italy
20Dept Academic Psychiatry, Bermondsey Wing Guys Hospital, University of London, UK
21Department of Psychology, Florida State University, Tallahassee, FL, USA
22Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
23Department of Psychology, Michigan State University, East Lansing, MI, USA
24Clinical Psychology Program, Argosy University, Washington, DC, USA
25Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
26Center for Health Sciences, SRI International, Menlo Park, CA, USA
27Brain Mind Institute, EPFLCH-1015 Lausanne, Switzerland
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Wang, K., Zhang, H., Bloss, C. et al. A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa. Mol Psychiatry 16, 949–959 (2011). https://doi.org/10.1038/mp.2010.107
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