e-Article
Evidence for the role of EPHX2 gene variants in anorexia nervosa
Document Type
article
Author
Scott-Van Zeeland, AA; Bloss, CS; Tewhey, R; Bansal, V; Torkamani, A; Libiger, O; Duvvuri, V; Wineinger, N; Galvez, L; Darst, BF; Smith, EN; Carson, A; Pham, P; Phillips, T; Villarasa, N; Tisch, R; Zhang, G; Levy, S; Murray, S; Chen, W; Srinivasan, S; Berenson, G; Brandt, H; Crawford, S; Crow, S; Fichter, MM; Halmi, KA; Johnson, C; Kaplan, AS; La Via, M; Mitchell, JE; Strober, M; Rotondo, A; Treasure, J; Woodside, DB; Bulik, CM; Keel, P; Klump, KL; Lilenfeld, L; Plotnicov, K; Topol, EJ; Shih, PB; Magistretti, P; Bergen, AW; Berrettini, W; Kaye, W; Schork, NJ
Source
Molecular Psychiatry. 19(6)
Subject
Language
Abstract
Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P