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

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.

The genetics of eating disorders.

The eating disorders anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder and allied diagnoses such as eating disorder not otherwise specified are common, complex psychiatric disorders with a significant genetic component. Aetiology is unknown, but both phenotypic characteristics and genetic factors appear to be shared across these disorders, and indeed patients often change between diagnostic categories. Molecular studies have attempted to define genetic risk factors for these disorders, including case-control and family-based candidate gene association studies and linkage analysis of multiply affected nuclear families. These have used both clinical diagnoses and eating disorder-related intermediate phenotypes such as drive-for-thinness or body dissatisfaction. Candidate gene studies have focussed on neurotransmitter and neurodevelopmental systems [e.g. serotonergic, opioid, cannabinoid and dopaminergic receptors, and brain-derived neurotrophic factor (BDNF)], appetite regulatory peptides and their receptors [leptin, ghrelin, agouti-related protein (AgRP), melanocortin receptors, neuropeptide Y], energy balance systems (e.g. uncoupling proteins), genes implicated in obesity (e.g. FTO) and sex hormone systems (e.g. oestrogen receptors), either identified on the basis of their function alone or as positional candidates from linkage analysis. Of these studies, linkage analysis implicates 1p33-36 for AN, 1q31.3 for quantitative behavioural traits related to anorexia and 10p14 for BN, as well as other behavioural phenotypes across both disorders. Candidate gene association has implicated BDNF, delta 1 opioid receptor (OPDR1) and AgRP. More recently, with the advent of genome-wide association studies (GWAS), analysis with microsatellite markers has implicated novel candidate loci for AN at 1q41 and 11q22, and further GWAS results are expected in the near future.