The 5-HT2A −1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres

Abstract

Keywords: eating disorder; serotonin; TDT (transmission disequilibrium test); QTL (quantitative trait loci)Several case-control association studies have raised the possibility that the A allele of a −1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar 2 = 0.29, df = 1, P = 0.59). Also, the haplotypebased haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre ( 2 Ͻ 2.15, df = 1, P Ͼ 0.14) and in the total sample ( 2 = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples ( 2 = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT 2A gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size). Molecular Psychiatry (2002) 7, 90-94.

Lifetime substance abuse, family history of alcohol abuse/dependence and novelty seeking in eating disorders: Comparison study of eating disorder subgroups

“…data, 2008). 4,29 The elevated novelty seeking scores found in the present bulimic groups (AN-BP and AN-Cross) may be related to the emergence of binge eating at some point during the course of the eating disturbance. 2,16,30 The use of behavioral models of binge eating and other feeding protocols is beginning to clarify the overlap between binge eating and substance use behaviors.…”

The Genetics of Anorexia Nervosa

“…To obtain a power of 80% under these assumptions, at least 178 cases and 178 controls are required. Only three association studies have been performed that had adequate statistical power to detect an effect (4,10,22); results of these studies are listed in the first section of Table 1. Two studies focused on the serotonin receptor 1D gene (4,10).…”

Combined family trio and case‐control analysis of the COMT Val158Met polymorphism in European patients with anorexia nervosa

“…The aim of this study is to attempt to replicate the finding of Frisch et al [2001] in family trios and case controls with AN from across Europe. The present study is part of a series of candidate gene studies on eating disorders using the same sample set [Gorwood et al, 2002].…”