A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling

被引：0

作者：

Dong Li

Xiao Chang

John J. Connolly

Lifeng Tian

Yichuan Liu

Elizabeth J. Bhoj

Nora Robinson

Debra Abrams

Yun R. Li

Jonathan P. Bradfield

Cecilia E. Kim

Jin Li

Fengxiang Wang

James Snyder

Maria Lemma

Cuiping Hou

Zhi Wei

Yiran Guo

Haijun Qiu

Frank D. Mentch

Kelly A. Thomas

Rosetta M. Chiavacci

Roger Cone

Bingshan Li

Patrick A. Sleiman

Hakon Hakonarson

机构：

[1] Children’s Hospital of Philadelphia,Center for Applied Genomics

[2] Vanderbilt University,Department of Molecular Physiology and Biophysics

[3] Children’s Hospital of Philadelphia,Department of Human Genetics

[4] The Perelman School of Medicine,Department of Pediatrics

[5] University of Pennsylvania,Department of Molecular and Integrative Physiology

[6] University of Michigan,Health Services Research Unit

[7] University of Aberdeen,William Harvey Research Institute

[8] Wellcome Trust Sanger Institute,Department of Psychiatry

[9] Wellcome Trust Genome Campus,Wellcome Trust Centre for Human Genetics (WTCHG)

[10] University of Split School of Medicine,Oxford Centre for Diabetes

[11] Barts and The London School of Medicine and Dentistry,Department of Psychology

[12] Queen Mary University of London,Section of Eating Disorders, Institute of Psychiatry

[13] John Vane Science Centre,Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Universitätsklinikum Essen

[14] University of North Carolina at Chapel Hill,INSERM U894

[15] University of Oxford,Sainte

[16] Endocrinology and Metabolism (OCDEM),Anne Hospital (CMME)

[17] Michigan State University,Brain Center Rudolf Magnus, Department of Translational Neuroscience

[18] King’s College London,Department of Neurosciences

[19] University of Duisburg-Essen,Department of Psychiatry and CIBERON

[20] Centre of Psychiatry and Neuroscience,Department of Clinical Sciences, School of Medicine

[21] University of Paris-Descartes,Genomics and Disease Group

[22] University Medical Center Utrecht,Department of Child and Adolescent Psychiatry

[23] Altrecht Eating Disorders Rintveld,Department of Child and Adolescent Psychiatry, Department of Psychiatry

[24] University of Padova,Hjelt Institute

[25] University Hospital of Bellvitge-IDIBELL,Institute of Molecular Medicine

[26] University of Barcelona,Department of Mental Health and Substance Abuse Services

[27] Centre for Genomic Regulation (CRG),Department of Adolescent Psychiatry

[28] Universitat Pompeu Fabra (UPF),Leiden University Medical Centre

[29] Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP),Department of Psychiatry

[30] Hospital del Mar Medical Research Institute (IMIM),Department of Genetics, Environment and Mental Health

[31] Institute of Psychiatry and Neurology,Institute of Clinical Medicine

[32] Poznan University of Medical Sciences,Department of Psychiatry

[33] University of Helsinki,Chair of Psychiatry

[34] University of Helsinki,Centre for Addiction and Mental Health

[35] National Institute for Health and Welfare,Department of Psychiatry

[36] Helsinki University Central Hospital,Eating Disorders Unit, Department of Child and Adolescent Psychiatry

[37] Center for Eating Disorders Ursula,Department of Psychiatry

[38] Department of Psychiatry,Department of Molecular and Experimental Medicine and The Scripps Translational Science Institute

[39] Leiden University Medical Centre,Department of Psychosomatic Research

[40] Molecular Epidemiology Section (Department of Medical Statistics),Department of Molecular Life Sciences

[41] McLean Hospital/Harvard Medical School,Estonian Genome Center

[42] Norwegian Institute of Public Health,Institute of Molecular and Cell Biology

[43] University of Oslo,Center for Integrative Genomics

[44] University of Naples SUN,Department of Genetics

[45] University of Salerno,Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry

[46] University of Toronto,UCL Genetics Institute, Department of Genetics, Evolution and Environment

[47] University of Toronto,Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy

[48] Medical University of Vienna,Department of Child and Adolescent Psychiatry

[49] University of Pennsylvania,Department of Psychosomatic Medicine and Psychotherapy

[50] The Scripps Research Institute,Department of Psychosomatic Medicine and Psychotherapy

来源：

Scientific Reports | / 7卷

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摘要：

We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10−7; OR = 0.7; 95% confidence interval (CI) = 0.61–0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

引用

共 50 条

[1] A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
Li, Dong
Chang, Xiao
Connolly, John J.
Tian, Lifeng
Liu, Yichuan
Bhoj, Elizabeth J.
Robinson, Nora
Abrams, Debra
Li, Yun R.
Bradfield, Jonathan P.
Kim, Cecilia E.
Li, Jin
Wang, Fengxiang
Snyder, James
Lemma, Maria
Hou, Cuiping
Wei, Zhi
Guo, Yiran
Qiu, Haijun
Mentch, Frank D.
Thomas, Kelly A.
Chiavacci, Rosetta M.
Cone, Roger
Li, Bingshan
Sleiman, Patrick A.
Hakonarson, Hakon
SCIENTIFIC REPORTS, 2017, 7
[2] Erratum: A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
Dong Li
Xiao Chang
John J. Connolly
Lifeng Tian
Yichuan Liu
Elizabeth J. Bhoj
Nora Robinson
Debra Abrams
Yun R. Li
Jonathan P. Bradfield
Cecilia E. Kim
Jin Li
Fengxiang Wang
James Snyder
Maria Lemma
Cuiping Hou
Zhi Wei
Yiran Guo
Haijun Qiu
Frank D. Mentch
Kelly A. Thomas
Rosetta M. Chiavacci
Roger Cone
Bingshan Li
Patrick A. Sleiman
Hakon Hakonarson
Scientific Reports, 7
[3] A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling (vol 7, 3847, 2017)
Li, Dong
Chang, Xiao
Connolly, John J.
Tian, Lifeng
Liu, Yichuan
Bhoj, Elizabeth J.
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Abrams, Debra
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Bradfield, Jonathan P.
Kim, Cecilia E.
Li, Jin
Wang, Fengxiang
Snyder, James
Lemma, Maria
Hou, Cuiping
Wei, Zhi
Guo, Yiran
Qiu, Haijun
Mentch, Frank D.
Thomas, Kelly A.
Chiavacci, Rosetta M.
Cone, Roger
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SCIENTIFIC REPORTS, 2017, 7
[4] A genome-wide association study of anorexia nervosa
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[10] GENOME-WIDE ASSOCIATION STUDIES OF ANOREXIA NERVOSA: AN OVERVIEW, UPDATE, AND IMPLICATIONS
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