Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Eating Disorders Working Group of the Psychiatric Genomics Consortium - (Autor:in)
  • Psychosoziale Medizin und Entwicklungsneurowissenschaften
  • Klinik und Poliklinik für Kinder- und Jugendpsychiatrie
  • Wellcome Sanger Institute
  • Icahn School of Medicine at Mount Sinai
  • University of North Carolina at Chapel Hill
  • King's College London (KCL)
  • University of Helsinki
  • Universitätsklinikum Frankfurt
  • Universität Duisburg-Essen
  • Universitätsklinikum Tübingen
  • Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
  • Medizinische Fakultät Carl Gustav Carus Dresden
  • Georgia State University
  • Erasmus University Rotterdam
  • Massachusetts General Hospital
  • Kartini Clinic
  • Utrecht University
  • INSERM - Institut national de la santé et de la recherche médicale
  • University of Michigan, Ann Arbor
  • Harokopio University
  • Rivierduinen Eating Disorders Ursula
  • National and Kapodistrian University of Athens
  • Harvard University
  • University of Toronto
  • University of Groningen
  • University of Aberdeen
  • Norwegian Institute of Public Health
  • Leiden University
  • Universita della Campania Luigi Vanvitelli
  • King Abdullah University of Science and Technology
  • University of Salerno
  • Boston University
  • University of Cyprus
  • Children's Hospital Panagiotis and Aglaia Kyriakou

Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6), and rs7700147, an intergenic variant (P=2.93 × 10 -5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Details

OriginalspracheEnglisch
Seiten (von - bis)1169-1180
Seitenumfang12
FachzeitschriftMolecular psychiatry
Jahrgang23
Ausgabenummer5
PublikationsstatusVeröffentlicht - 1 Mai 2018
Peer-Review-StatusJa

Externe IDs

PubMed 29155802
ORCID /0000-0003-2132-4445/work/160950909