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

L. M. Huckins; K. Hatzikotoulas; L. Southam; L. M. Thornton; J. Steinberg; F. Aguilera-McKay; J. Treasure; U. Schmidt; C. Gunasinghe; A. Romero; C. Curtis; D. Rhodes; J. Moens; G. Kalsi; D. Dempster; R. Leung; A. Keohane; R. Burghardt; S. Ehrlich; J. Hebebrand; A. Hinney; A. Ludolph; E. Walton; P. Deloukas; A. Hofman; A. Palotie; P. Palta; F. J. A. van Rooij; K. Stirrups; R. Adan; C. Boni; R. Cone; G. Dedoussis; E. van Furth; F. Gonidakis; P. Gorwood; J. Hudson; J. Kaprio; M. Kas; A. Keski-Rahonen; K. Kiezebrink; G-P Knudsen; M. C. T. Slof-Op 't Landt; M. Maj; A. M. Monteleone; P. Monteleone; A. H. Raevuori; T. Reichborn-Kjennerud; F. Tozzi; A. Tsitsika; A. van Elburg; D. A. Collier; P. F. Sullivan; G. Breen; C. M. Bulik; E. Zeggini; Eating Disorder Working Grp Psych

doi:10.1038/mp.2017.88

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

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

L. M. Huckins, K. Hatzikotoulas, L. Southam, L. M. Thornton, J. Steinberg, F. Aguilera-McKay, J. Treasure, U. Schmidt, C. Gunasinghe, A. Romero, …

Molecular psychiatry, Vol.23(5), pp.1169-1180

01/05/2018

DOI: https://doi.org/10.1038/mp.2017.88

PMCID: PMC5828108

PMID: 29155802

Abstract

Biochemistry & Molecular Biology

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

Psychiatry

Science & Technology

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 x 10(-6)), and rs7700147, an intergenic variant (P = 2.93 x 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.

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Title: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa
Creators - without role: L. M. Huckins - Wellcome Sanger Institute
K. Hatzikotoulas - Wellcome Sanger Institute
L. Southam - Wellcome Sanger Institute
L. M. Thornton - University of North Carolina at Chapel Hill
J. Steinberg - Wellcome Sanger Institute
F. Aguilera-McKay - Wellcome Sanger Institute
J. Treasure - King's College London
U. Schmidt - King's College London
C. Gunasinghe - King's College London
A. Romero - King's College London
C. Curtis - King's College London
D. Rhodes - King's College London
J. Moens - King's College London
G. Kalsi - King's College London
D. Dempster - King's College London
R. Leung - King's College London
A. Keohane - King's College London
R. Burghardt - Klin Kinder & Jugendpsychiatrie, Psychotherapie & Psychosomat Klinikum Frankfurt, Frankfurt, Germany
S. Ehrlich - TU Dresden
J. Hebebrand - University of Duisburg-Essen
A. Hinney - University of Duisburg-Essen
A. Ludolph - Helmholtz Zentrum München
E. Walton - TU Dresden
P. Deloukas - Wellcome Sanger Institute
A. Hofman - Erasmus MC
A. Palotie - Massachusetts General Hospital
P. Palta - Institute for Molecular Medicine Finland
F. J. A. van Rooij - Erasmus MC
K. Stirrups - Wellcome Sanger Institute
R. Adan - University Medical Center Utrecht
C. Boni - Institute of Psychiatry and Neuroscience of Paris
R. Cone - University of Michigan–Ann Arbor
G. Dedoussis - Harokopio University of Athens
E. van Furth - GGZ Rivierduinen
F. Gonidakis - National and Kapodistrian University of Athens
P. Gorwood - Institute of Psychiatry and Neuroscience of Paris
J. Hudson - McLean Hospital
J. Kaprio - Institute for Molecular Medicine Finland
M. Kas - University of Groningen
A. Keski-Rahonen - University of Helsinki
K. Kiezebrink - University of Aberdeen
G-P Knudsen - Norwegian Institute of Public Health
M. C. T. Slof-Op 't Landt - Rivierduinen Eating Disorders Ursula, Leiden, Zuid Holland, Netherlands
M. Maj - University of Naples Federico II
A. M. Monteleone - University of Salerno
P. Monteleone - University of Salerno
A. H. Raevuori - University of Helsinki
T. Reichborn-Kjennerud - Norwegian Institute of Public Health
F. Tozzi - University of Cyprus
A. Tsitsika - Panagiotis & Aglaia Kyriakou Children's Hospital
A. van Elburg - Utrecht University
D. A. Collier - Eli Lilly
P. F. Sullivan - University of North Carolina at Chapel Hill
G. Breen - King's College London
C. M. Bulik - University of North Carolina at Chapel Hill
E. Zeggini - Wellcome Sanger Institute
Eating Disorder Working Grp Psych
Publication Details: Molecular psychiatry, Vol.23(5), pp.1169-1180
Publisher: Springer Nature
Number of pages: 12
Grant note: Economic and Social Research Council; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF)-Research Funding Program: Heracleitus II MR/J500355/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 980 / Maudsley Charity STR130505 / Guy's and St Thomas's Charity Dnr: 538-2013-8864 / Swedish Research Council (VR); Swedish Research Council 263278 / Academy of Finland; Research Council of Finland Wa 3635/1-1 / German Research Foundation; German Research Foundation (DFG) Klarman Family Foundation National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and King's College London ES/H029745/1 / ESRC; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) ES/H029745/1 / Economic and Social Research Council; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) K01MH109782; R01MH085542; R01MH093725; P50MH066392; P50MH080405; R01MH097276; R01-MH-075916; P50M096891; P50MH084053S1; R37MH057881; R37MH057881S1; HHSN271201300031C; AG02219; AG05138; MH06692 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 098051 / Wellcome Trust European Union (European Social Fund-ESF); European Social Fund (ESF); European Commission Takeda Pharmaceuticals Company Limited
Identifiers: 9938148308331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article