Genome‐wide association analysis of eating disorder‐related symptoms, behaviors, and personality traits

Abstract

Eating disorders (EDs) are common, complex psychiatric disorders thought to be caused by both genetic and environmental factors. They share many symptoms, behaviors, and personality traits, which may have overlapping heritability. The aim of the present study is to perform a genome-wide association scan (GWAS) of six ED phenotypes comprising three symptom traits from the Eating Disorders Inventory 2 [Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia], Weight Fluctuation symptom, Breakfast Skipping behavior and Childhood Obsessive-Compulsive Personality Disorder trait (CHIRP). Investigated traits were derived from standardized self-report questionnaires completed by the TwinsUK population-based cohort. We tested 283,744 directly typed SNPs across six phenotypes of interest in the TwinsUK discovery dataset and followed-up signals from various strata using a two-stage replication strategy in two independent cohorts of European ancestry. We meta-analyzed a total of 2,698 individuals for DT, 2,680 for BD, 2,789 (821 cases/1,968 controls) for Bulimia, 1,360 (633 cases/727 controls) for Childhood Obsessive-Compulsive Personality Disorder trait, 2,773 (761 cases/2,012 controls) for Breakfast Skipping, and 2,967 (798 cases/2,169 controls) for Weight Fluctuation symptom. In this GWAS analysis of six ED-related phenotypes, we detected association of eight genetic variants with P < 10−5. Genetic variants that showed suggestive evidence of association were previously associated with several psychiatric disorders and ED-related phenotypes. Our study indicates that larger-scale collaborative studies will be needed to achieve the necessary power to detect loci underlying ED-related traits. © 2012 Wiley Periodicals, Inc.

A genome-wide association study of anorexia nervosa

“…Twelve out of 14 variants previously reported to be associated with eating disorder-related symptoms, behaviors, and personality traits 59, 60 were found in our discovery meta-analysis and 7 had the same direction of effect (P=0.774) (Table S10), with one SNP (inside RUFY1 ) having P<0.05 (binomial P=0.459). We did not find evidence for signal enrichment in the 60 independent SNPs found in the Psychiatric Genomics Consortium data for ADHD, schizophrenia, bipolar disorder, or major depressive disorder 63-66 (Table S11).…”

“…Only two SNPs, rs1523921 (also found to be suggestively associated in the main case-control analysis) and rs10777211 located 333kb upstream of ATP2B1 , showed association at the 10 -5 significance level (Table S6). Similarly, subsequent analyses pertaining to associated phenotypes (weight regulation: BMI/obesity loci, 40, 61, 69, 70 and loci for extreme obesity; 61, 71, 72 psychiatric comorbidities: ADHD, schizophrenia, bipolar disorder, and major depressive disorder) or previous equivocal association findings for AN or eating disorders (AN variants, 42 eating disorder related symptoms, behaviors, and personality traits variants 59, 60 ) did not reveal significant findings. More adequately powered analyses that could allow us to detect variants that can distinguish between these two subtypes could be clinically meaningful in predicting clinical course and outcome and eventually in designing targeted therapeutics.…”

“…Using the discovery meta-analysis, we investigated evidence for association using SNP results from published studies: 9 SNPs with nominal evidence of association with AN; 42 14 SNPs suggestively associated with eating disorder-related symptoms, behaviors, or personality traits; 59, 60 89 SNPs with genome-wide significance in studies of BMI or obesity; 61, 62 and 15 SNPs related to morbid obesity. 61 We also investigated evidence for association across the 72 replication SNPs using published GWAS results from the Psychiatric Genomics Consortium (https://pgc.unc.edu) for attention-deficit/hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, and major depressive disorder.…”

An Evolutionary Genetic Perspective of Eating Disorders

“…A recent negative two-stage GWAS meta-analysis for AN in 5,551 cases and 21,080 controls concluded that the accrual of large genotyped AN case-control samples should be an immediate priority for the field to identify AN-predisposing genes [81]. Although there were no genome-wide significant hits reported, 72 independent markers with the lowest p values were selected for replication in an independent sample, and 76% of these loci produced results directionally consistent with the discovery sample [82].…”

Advances in the neurobiology of eating disorders

“…For example, a GWAS study of eating disorder-related phenotypes found very weak signals; however, some of these had been implicated in previous studies [24].…”