Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Cristen J. Willer; Elizabeth K. Speliotes; Ruth J. F. Loos; Shengxu Li; Cecilia M. Lindgren; Iris M. Heid; Sonja I. Berndt; Amanda L. Elliott; Anne U. Jackson; Claudia Lamina; Guillaume Lettre; Noha Lim; Helen N. Lyon; Steven A. McCarroll; Konstantinos Papadakis; Lu Qi; Joshua C. Randall; Rosa Maria Roccasecca; Serena Sanna; Paul Scheet; Michael N. Weedon; Eleanor Wheeler; Jing Hua Zhao; Leonie C. Jacobs; Inga Prokopenko; Nicole Soranzo; Toshiko Tanaka; Nicholas J. Timpson; Peter Almgren; Amanda Bennett; Richard N. Bergman; Sheila A. Bingham; Lori L. Bonnycastle; Morris Brown; Noel L. P. Burtt; Peter Chines; Lachlan Coin; Francis S. Collins; John M. Connell; Cyrus Cooper; George Davey Smith; Elaine M. Dennison; Parimal Deodhar; Paul Elliott; Michael R. Erdos; Karol Estrada; David M. Evans; Lauren Gianniny; Christian Gieger; Christopher J. Gillson; Candace Guiducci; Rachel Hackett; David Hadley; Alistair S. Hall; Aki S. Havulinna; Johannes Hebebrand; Albert Hofman; Bo Isomaa; Kevin B. Jacobs; Toby Johnson; Pekka Jousilahti; Zorica Jovanovic; Kay-Tee Khaw; Peter Kraft; Mikko Kuokkanen; Johanna Kuusisto; Jaana Laitinen; Edward G. Lakatta; Jian'an Luan; Robert N. Luben; Massimo Mangino; Wendy L. McArdle; Thomas Meitinger; Antonella Mulas; Patricia B. Munroe; Narisu Narisu; Andrew R. Ness; Kate Northstone; Stephen O'Rahilly; Carolin Purmann; Matthew G. Rees; Martin Ridderstrale; Susan M. Ring; Fernando Rivadeneira; Aimo Ruokonen; Manjinder S. Sandhu; Jouko Saramies; Laura J. Scott; Angelo Scuteri; Kaisa Silander; Matthew A. Sims; Kijoung Song; Jonathan Stephens; Suzanne Stevens; Heather M. Stringham; Y. C. Loraine Tung; Timo T. Valle; Cornelia M. Van Duijn; Karani S. Vimaleswaran; Peter Vollenweider; Gerard Waeber; Chris Wallace; Richard M. Watanabe; Dawn M. Waterworth; Nicholas Watkins; Jacqueline C. M. Witteman; Eleftheria Zeggini; Guangju Zhai; M. Carola Zillikens; David Altshuler; Mark J. Caulfield; Stephen J. Chanock; I. Sadaf Farooqi; Luigi Ferrucci; Jack M. Guralnik; Andrew T. Hattersley; Frank B. Hu; Marjo-Riitta Jarvelin; Markku Laakso; Vincent Mooser; Ken K. Ong; Willem H. Ouwehand; Veikko Salomaa; Nilesh J. Samani; Timothy D. Spector; Tiinamaija Tuomi; Jaakko Tuomilehto; Manuela Uda; Andre G. Uitterlinden; Nicholas J. Wareham; Panagiotis Deloukas; Timothy M. Frayling; Leif C. Groop; Richard B. Hayes; David J. Hunter; Karen L. Mohlke; Leena Peltonen; David Schlessinger; David P. Strachan; H-Erich Wichmann; Mark I. McCarthy; Michael Boehnke; Ines Barroso; Goncalo R. Abecasis; Joel N. Hirschhorn; Wellcome Trust Case Control

doi:10.1038/ng.287

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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Journal article

Peer reviewed

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Cristen J. Willer, Elizabeth K. Speliotes, Ruth J. F. Loos, Shengxu Li, Cecilia M. Lindgren, Iris M. Heid, Sonja I. Berndt, Amanda L. Elliott, Anne U. Jackson, Claudia Lamina, …

Nature genetics, Vol.41(1), pp.25-34

01/01/2009

DOI: https://doi.org/10.1038/ng.287

PMCID: PMC2695662

PMID: 19079261

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

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Title: Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
Creators - without role: Cristen J. Willer - Biostat
Elizabeth K. Speliotes - Massachusetts Institute of Technology
Ruth J. F. Loos - Massachusetts Rehabilitation Commission
Shengxu Li - Massachusetts Rehabilitation Commission
Cecilia M. Lindgren - University of Oxford
Iris M. Heid - Helmholtz Zentrum München
Sonja I. Berndt - National Institutes of Health
Amanda L. Elliott - Broad Institute
Anne U. Jackson - University of Michigan–Ann Arbor
Claudia Lamina
Guillaume Lettre - Broad Institute
Noha Lim
Helen N. Lyon - Massachusetts Institute of Technology
Steven A. McCarroll - Broad Institute
Konstantinos Papadakis - St George's, University of London
Lu Qi - Harvard University
Joshua C. Randall - University of Oxford
Rosa Maria Roccasecca - Wellcome Sanger Institute
Serena Sanna - National Academies of Sciences, Engineering, and Medicine
Paul Scheet - University of Michigan–Ann Arbor
Michael N. Weedon - Supreme Council Of Health
Eleanor Wheeler - Wellcome Sanger Institute
Jing Hua Zhao - Massachusetts Rehabilitation Commission
Leonie C. Jacobs - Erasmus University Rotterdam
Inga Prokopenko - University of Oxford
Nicole Soranzo - King's College London
Toshiko Tanaka - National Institutes of Health
Nicholas J. Timpson - University of Bristol
Peter Almgren - Lund University
Amanda Bennett - Churchill Hospital
Richard N. Bergman - University of Southern California
Sheila A. Bingham - Wellcome Trust
Lori L. Bonnycastle - National Institutes of Health
Morris Brown - University of Cambridge
Noel L. P. Burtt - Broad Institute
Peter Chines - National Institutes of Health
Lachlan Coin - Imperial College London
Francis S. Collins - National Institutes of Health
John M. Connell - University of Glasgow
Cyrus Cooper - Southampton General Hospital
George Davey Smith - University of Bristol
Elaine M. Dennison - Southampton General Hospital
Parimal Deodhar - National Institutes of Health
Paul Elliott - Imperial College London
Michael R. Erdos - National Institutes of Health
Karol Estrada - Erasmus University Rotterdam
David M. Evans - University of Bristol
Lauren Gianniny - Broad Institute
Christian Gieger - Helmholtz Zentrum München
Christopher J. Gillson - Cambridge University Hospitals NHS Foundation Trust
Candace Guiducci - Broad Institute
Rachel Hackett - Broad Institute
David Hadley - St George's, University of London
Alistair S. Hall - Leeds General Infirmary
Aki S. Havulinna - Finnish Institute for Health and Welfare
Johannes Hebebrand - University of Duisburg-Essen
Albert Hofman - Erasmus University Rotterdam
Bo Isomaa - Malmska Municipal Hlth Ctr & Hosp, Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland
Kevin B. Jacobs - Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA
Toby Johnson - SIB Swiss Institute of Bioinformatics
Pekka Jousilahti - Finnish Institute for Health and Welfare
Zorica Jovanovic - University of Cambridge
Kay-Tee Khaw - University of Cambridge
Peter Kraft - Harvard University
Mikko Kuokkanen - Finnish Institute for Health and Welfare
Johanna Kuusisto - University of Eastern Finland
Jaana Laitinen - Finnish Institute of Occupational Health
Edward G. Lakatta - National Institutes of Health
Jian'an Luan - Cambridge University Hospitals NHS Foundation Trust
Robert N. Luben - University of Cambridge
Massimo Mangino - University of Leicester
Wendy L. McArdle - University of Bristol
Thomas Meitinger - Technical University of Munich
Antonella Mulas - National Academies of Sciences, Engineering, and Medicine
Patricia B. Munroe - Queen Mary University of London
Narisu Narisu - National Institutes of Health
Andrew R. Ness - University of Bristol
Kate Northstone - University of Bristol
Stephen O'Rahilly - University of Cambridge
Carolin Purmann - University of Cambridge
Matthew G. Rees - National Institutes of Health
Martin Ridderstrale - Lund University
Susan M. Ring - University of Bristol
Fernando Rivadeneira - Erasmus University Rotterdam
Aimo Ruokonen - University of Oulu
Manjinder S. Sandhu - University of Cambridge
Jouko Saramies - Savitaipale Hlth Ctr, FIN-54800 Savitaipale, Finland
Laura J. Scott - University of Michigan–Ann Arbor
Angelo Scuteri - Ist Nazl Ricovero & Cura Anziani, Unita Operat Geriatria, I-00189 Rome, Italy
Kaisa Silander - Finnish Institute for Health and Welfare
Matthew A. Sims - Cambridge University Hospitals NHS Foundation Trust
Kijoung Song
Jonathan Stephens - NHS Blood and Transplant
Suzanne Stevens - University of Leicester
Heather M. Stringham - University of Michigan–Ann Arbor
Y. C. Loraine Tung - University of Cambridge
Timo T. Valle - Finnish Institute for Health and Welfare
Cornelia M. Van Duijn - Erasmus University Rotterdam
Karani S. Vimaleswaran - University of Cambridge
Peter Vollenweider - University of Lausanne
Gerard Waeber
Chris Wallace - William Harvey Research Institute
Richard M. Watanabe - Biostat
Dawn M. Waterworth
Nicholas Watkins - University of Cambridge
Jacqueline C. M. Witteman
Eleftheria Zeggini - University of Oxford
Guangju Zhai - Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
M. Carola Zillikens - College Station Medical Center
David Altshuler - Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
Mark J. Caulfield - William Harvey Research Institute
Stephen J. Chanock - NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA
I. Sadaf Farooqi - Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 0QQ, England
Luigi Ferrucci - NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA
Jack M. Guralnik - NIA, Lab Epidemiol Demog & Biometry, Gerontol Res Ctr, Bethesda, MD 20892 USA
Andrew T. Hattersley - Supreme Council Of Health
Frank B. Hu - Harvard University
Marjo-Riitta Jarvelin - University of London
Markku Laakso - College Station Medical Center
Vincent Mooser
Ken K. Ong - Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 0QQ, England
Willem H. Ouwehand - Wellcome Sanger Institute
Veikko Salomaa - Natl Publ Hlth Inst, KTL, FI-00300 Helsinki, Finland
Nilesh J. Samani - University of Leicester
Timothy D. Spector - Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England
Tiinamaija Tuomi
Jaakko Tuomilehto
Manuela Uda - CNR, Inst Neurogenet & Neurofarmacol, I-09042 Cagaliai, Italy
Andre G. Uitterlinden - College Station Medical Center
Nicholas J. Wareham - Massachusetts Rehabilitation Commission
Panagiotis Deloukas - Wellcome Sanger Institute
Timothy M. Frayling - Supreme Council Of Health
Leif C. Groop - Lund University
Richard B. Hayes - NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA
David J. Hunter - Broad Institute
Karen L. Mohlke - Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
Leena Peltonen - Broad Institute
David Schlessinger - NIA, US Natl Inst Hlth Biomed Res Ctr, Genet Lab, Baltimore, MD 21224 USA
David P. Strachan - University of London
H-Erich Wichmann - Helmholtz Zentrum München
Mark I. McCarthy - University of Oxford
Michael Boehnke - Biostat
Ines Barroso - Wellcome Sanger Institute
Goncalo R. Abecasis - Biostat
Joel N. Hirschhorn - Massachusetts Institute of Technology
Wellcome Trust Case Control
Publication Details: Nature genetics, Vol.41(1), pp.25-34
Publisher: Springer Nature
Number of pages: 10
Grant note: 090532; 068545/Z/02; 077016; 089061; 076113; 076467/Z/05/Z; 079557; 077011; 082390 / Wellcome Trust; European Commission Z01HG000024 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) T32 DK007191; R56 DK062370; R01 DK075787; DK072193; F32 DK079466; U01 DK062370; DK075787; K23 DK080145; DK062370; R01 DK072193; K23 DK080145-01; R01 DK062370; F32 DK079466-01; K23 DK067288; R01 DK029867; T32DK07191 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) N01-AG-1-2109 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) NF-SI-0508-10082 / National Institute for Health Research; National Institute for Health Research (NIHR) R01HL087679 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) U01 CA098233; U01 CA049449; R01 CA065725; R01 CA050385; 5UO1CA098233; U01 CA067262; CA87969; CA67262; CA65725; R01 CA067262; R01 CA049449; CA50385; CA49449; P01 CA087969 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U1475000001 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission HG02651; 01-HG-65403; R01 HG002651; N01HG65403; 1Z01 HG000024 / NHGRI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) P01CA087969 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) K23DK080145 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) MC_U106179471; MC_UP_A620_1014; G0401527; G0400874; G0000649; G9824984; U.1475.00.003.00010.02 (85819); MC_U147585827; G9521010; G0601261; G0800582; G9815508; MC_U147585824; MC_U106188470; G0000934; MC_U106179472; MC_U147585819; G0400491; MC_U105630924; G0701863; G0600705 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission RL1MH083268 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01 HL087679; HL084729; HL087679; U01 HL084729 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) ZIAAG000799 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) FS/05/061/19501 / British Heart Foundation RL1 MH083268; 1RL1MH083268 / NIMH NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) Z01 HG000024 / Intramural NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA G9521010 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 9939579808331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article