CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
Aurélien Macé(SIB Swiss Institute of Bioinformatics), Marcus A. Tuke(University of Exeter), Patrick Deelen(University Medical Center Groningen), Kati Kristiansson(University of Helsinki), Hannele Mattsson(University of Helsinki), Margit Nõukas(University of Tartu), Yadav Sapkota(St. Jude Children's Research Hospital), Ursula M. Schick(Icahn School of Medicine at Mount Sinai), Eleonora Porcu(SIB Swiss Institute of Bioinformatics), Sina Rüeger(SIB Swiss Institute of Bioinformatics), Aaron F. McDaid(SIB Swiss Institute of Bioinformatics), David J. Porteous(Edinburgh Cancer Research), Thomas W. Winkler(University of Regensburg), Erika Salvi(University of Milan), Nick Shrine(University of Leicester), Xueping Liu(Statens Serum Institut), Wei Ang(Women and Infants Research Foundation), Weihua Zhang(Ealing Hospital), Mary F. Feitosa(Washington University in St. Louis), Cristina Venturini(King's College London), Peter J. van der Most(University Medical Center Groningen), Anders Rosengren(Sankt Hans Hospital), Andrew R. Wood(University of Exeter), Robin N. Beaumont(University of Exeter), Samuel E. Jones(University of Exeter), Katherine S. Ruth(University of Exeter), Hanieh Yaghootkar(University of Exeter), Jessica Tyrrell(University of Exeter), Aki S. Havulinna(Finnish Institute for Health and Welfare), Harmen Boers(University Medical Center Groningen), Reedik Mägi(University of Tartu), Jennifer Kriebel(Helmholtz Zentrum München), Martina Müller‐Nurasyid(Helmholtz Zentrum München), Markus Perola(Finnish Institute for Health and Welfare), Markku S. Nieminen, Marja‐Liisa Lokki(University of Helsinki), Mika Kähönen(Tampere University Hospital), Jorma Viikari(University of Turku), Frank Geller(Statens Serum Institut), Jari Lahti(University of Helsinki), Aarno Palotie(Broad Institute), Päivikki Koponen(Finnish Institute for Health and Welfare), Annamari Lundqvist(Finnish Institute for Health and Welfare), Harri Rissanen(Finnish Institute for Health and Welfare), Erwin P. Böttinger(Icahn School of Medicine at Mount Sinai), Saima Afaq(Imperial College London), Mary K. Wojczynski(Washington University in St. Louis), Petra Lenzini(Washington University in St. Louis), Ilja M. Nolte(University Medical Center Groningen), Thomas Sparsø(Sankt Hans Hospital), Nicole Schupf(Columbia University), Kaare Christensen(University of Southern Denmark), Thomas T. Perls(Boston University), Anne B. Newman(University of Pittsburgh), Thomas Werge(University of Copenhagen), Harold Snieder(University Medical Center Groningen), Timothy D. Spector(King's College London), John C. Chambers(Imperial College Healthcare NHS Trust), Seppo Koskinen(Finnish Institute for Health and Welfare), Mads Melbye(Statens Serum Institut), Olli T. Raitakari(University of Turku), Terho Lehtimäki(Tampere University), Martin D. Tobin(University of Leicester), Louise V. Wain(University of Leicester), Juha Sinisalo, Annette Peters(Helmholtz Zentrum München), Thomas Meitinger(Helmholtz Zentrum München), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Naomi R. Wray(The University of Queensland), Grant W. Montgomery(The University of Queensland), Sarah E. Medland(QIMR Berghofer Medical Research Institute), Morris A. Swertz(University Medical Center Groningen), Erkki Vartiainen(Finnish Institute for Health and Welfare), Katja Borodulin(Finnish Institute for Health and Welfare), Satu Männistö(Finnish Institute for Health and Welfare), Anna Murray(University of Exeter), Murielle Bochud(Institute of Social and Preventive Medicine), Sébastien Jacquemont(Centre Hospitalier Universitaire Sainte-Justine), Fernando Rivadeneira(Erasmus MC), Thomas Folkmann Hansen(Sankt Hans Hospital), Albertine J. Oldehinkel(University Medical Center Groningen), Massimo Mangino(King's College London), Michael A. Province(Washington University in St. Louis), Panos Deloukas(Queen Mary University of London), Jaspal S. Kooner(Imperial College Healthcare NHS Trust), Rachel M. Freathy(University of Exeter), Craig E. Pennell(Women and Infants Research Foundation), Bjarke Feenstra(Statens Serum Institut), David P. Strachan(St George's, University of London), Guillaume Lettre(Montreal Heart Institute), Joel N. Hirschhorn(Broad Institute), Daniele Cusi(University of Milan), Iris M. Heid(University of Regensburg), Caroline Hayward(Institute of Genetics and Cancer), Katrin Männik(University of Tartu), J. Beckmann(SIB Swiss Institute of Bioinformatics), Ruth J. F. Loos(Icahn School of Medicine at Mount Sinai), Dale R. Nyholt(Queensland University of Technology), Andres Metspalu(University of Tartu), Johan G. Eriksson(University of Helsinki), Michael N. Weedon(University of Exeter), Veikko Salomaa(Finnish Institute for Health and Welfare), Lude Franke(University Medical Center Groningen), Alexandre Reymond(University of Lausanne), Timothy M. Frayling(University of Exeter), Zoltán Kutalik(SIB Swiss Institute of Bioinformatics)
Cited by 105Open Access
Abstract
Abstract There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01–0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m 2 ). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m 2 for each Mb of total deletion burden ( P = 2.5 × 10 −10 , 6.0 × 10 −5 , and 2.9 × 10 −3 ). Our study provides evidence that the same genes (e.g., MC4R , FIBIN , and FMO5 ) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.
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