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Evidence for the role of EPHX2 gene variants in anorexia nervosa

Academic Article
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Overview

authors

  • Scott-Van Zeeland, A. A.
  • Bloss, C. S.
  • Tewhey, R.
  • Bansal, V.
  • Torkamani, Ali
  • Libiger, O.
  • Duvvuri, V.
  • Wineinger, Nathan
  • Galvez, L.
  • Darst, B. F.
  • Smith, E. N.
  • Carson, A.
  • Pham, P.
  • Phillips, T.
  • Villarasa, N.
  • Tisch, R.
  • Zhang, G.
  • Levy, Samuel
  • Murray, Sarah
  • Chen, W.
  • Srinivasan, S.
  • Berenson, G.
  • Brandt, H.
  • Crawford, S.
  • Crow, S.
  • Fichter, M. M.
  • Halmi, K. A.
  • Johnson, C.
  • Kaplan, A. S.
  • La Via, M.
  • Mitchell, J. E.
  • Strober, M.
  • Rotondo, A.
  • Treasure, J.
  • Woodside, D. B.
  • Bulik, C. M.
  • Keel, P.
  • Klump, K. L.
  • Lilenfeld, L.
  • Plotnicov, K.
  • Topol, Eric
  • Shih, P. B.
  • Magistretti, P.
  • Bergen, A. W.
  • Berrettini, W.
  • Kaye, W.
  • Schork, Nicholas

publication date

  • 2014

journal

  • Molecular Psychiatry  Journal

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<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.

subject areas

  • Adult
  • Anorexia Nervosa
  • Body Mass Index
  • Case-Control Studies
  • Cholesterol
  • Cohort Studies
  • Epoxide Hydrolases
  • European Continental Ancestry Group
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Psychometrics
  • Young Adult
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Identity

PubMed Central ID

  • PMC3852189

International Standard Serial Number (ISSN)

  • 1359-4184

Digital Object Identifier (DOI)

  • 10.1038/mp.2013.91

PubMed ID

  • 23999524
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Additional Document Info

start page

  • 724

end page

  • 732

volume

  • 19

issue

  • 6

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