Association study of 182 candidate genes in anorexia nervosa

Abstract

We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case-control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN NIH Public AccessAuthor Manuscript Am J Med Genet B Neuropsychiatr Genet. Author manuscript; available in PMC 2010 October 25. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathwaybased analysis in order to make up for deficiencies in traditional candidate gene approaches to AN.

No association of brain‐derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese

“…The lifetime diagnosis and sub-typing of AN were made according to the criteria of Pinheiro et al [2010] in which amenorrhea is not required for any AN diagnosis. Using their criteria, 357 patients were categorized as AN restricting subtype (RAN), 39 were AN purging subtype (PAN), 195 were AN with binge eating (BAN), and 121 were lifetime AN and bulimia nervosa (ANBN).…”

Eating disorder predisposition is associated with ESRRA and HDAC4 mutations

“…EDs are thought to occur as a result of a complex interaction between genetic predisposition and environmental risk factors. While genetic factors are estimated to contribute 50%-80% of the risk of developing an ED (2), to date, several studies using both genome-wide analysis (3,4) and candidate gene (5) approaches have failed to identify specific genes that predispose to the development of an ED. One alternative approach to large-scale linkage and association studies is to characterize rare single-gene mutations in large families severely affected by mental illness.…”

Identificação de polimorfismos de genes candidatos nos transtornos alimentares

“…27 Em outra pesquisa, testou-se 5.151 SNPs em 1085 indivíduos com diagnóstico de TAs e 677 indivíduos saudáveis, sem resultado significativo dos SNPs nos alelos. 28 30 Em outro estudo, ao estimar a prevalência desse SNP em 182 pacientes japoneses com TAs, observou que a frequência do alelo G do lócus 5HT 2A foi muito maior naqueles com TA do que no grupo controle (GC), cuja diferença na frequência do alelo G foi de 0,09 (0,55-0,46). Nos pacientes com BN, a frequên-cia do alelo G foi muito mais elevada do que no GC (0,10; 0,56-0,46).…”