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

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

Abstract 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...

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Autores principales: 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, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Price Foundation Collaborative Group, Hakon Hakonarson
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/c8e31ccf3a9142b0b22d33ac699f7142
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spelling oai:doaj.org-article:c8e31ccf3a9142b0b22d33ac699f71422021-12-02T12:30:18ZA genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling10.1038/s41598-017-01674-82045-2322https://doaj.org/article/c8e31ccf3a9142b0b22d33ac699f71422017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01674-8https://doaj.org/toc/2045-2322Abstract 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.Dong LiXiao ChangJohn J. ConnollyLifeng TianYichuan LiuElizabeth J. BhojNora RobinsonDebra AbramsYun R. LiJonathan P. BradfieldCecilia E. KimJin LiFengxiang WangJames SnyderMaria LemmaCuiping HouZhi WeiYiran GuoHaijun QiuFrank D. MentchKelly A. ThomasRosetta M. ChiavacciRoger ConeBingshan LiPatrick A. SleimanEating Disorders Working Group of the Psychiatric Genomics ConsortiumPrice Foundation Collaborative GroupHakon HakonarsonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Eating Disorders Working Group of the Psychiatric Genomics Consortium
Price Foundation Collaborative Group
Hakon Hakonarson
A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
description Abstract 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.
format article
author 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
Eating Disorders Working Group of the Psychiatric Genomics Consortium
Price Foundation Collaborative Group
Hakon Hakonarson
author_facet 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
Eating Disorders Working Group of the Psychiatric Genomics Consortium
Price Foundation Collaborative Group
Hakon Hakonarson
author_sort Dong Li
title A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
title_short A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
title_full A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
title_fullStr A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
title_full_unstemmed A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
title_sort genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/c8e31ccf3a9142b0b22d33ac699f7142
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