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CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Author

Listed:
  • Aurélien Macé

    (Lausanne University Hospital
    Swiss Institute of Bioinformatics
    University of Lausanne)

  • Marcus A. Tuke

    (University of Exeter Medical School, University of Exeter)

  • Patrick Deelen

    (University of Groningen, University Medical Center Groningen
    University of Groningen, University Medical Center Groningen, Genomics Coordination Center)

  • Kati Kristiansson

    (National Institute for Health and Welfare
    University of Helsinki)

  • Hannele Mattsson

    (National Institute for Health and Welfare
    University of Helsinki)

  • Margit Nõukas

    (University of Tartu
    University of Tartu)

  • Yadav Sapkota

    (QIMR Berghofer Medical Research Institute
    St. Jude Children’s Research hospital)

  • Ursula Schick

    (Icahn School of Medicine at Mount Sinai)

  • Eleonora Porcu

    (Swiss Institute of Bioinformatics
    University of Lausanne)

  • Sina Rüeger

    (Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • Aaron F. McDaid

    (Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • David Porteous

    (University of Edinburgh)

  • Thomas W. Winkler

    (University of Regensburg)

  • Erika Salvi

    (University of Milano)

  • Nick Shrine

    (University of Leicester)

  • Xueping Liu

    (Statens Serum Institut)

  • Wei Q. Ang

    (The University of Western Australia)

  • Weihua Zhang

    (Imperial College London
    Ealing Hospital NHS Trust)

  • Mary F. Feitosa

    (Washington University School of Medicine)

  • Cristina Venturini

    (King’s College London)

  • Peter J. Most

    (University of Groningen, University Medical Center Groningen)

  • Anders Rosengren

    (Mental Health Center Sct. Hans
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Andrew R. Wood

    (University of Exeter Medical School, University of Exeter)

  • Robin N. Beaumont

    (University of Exeter Medical School, University of Exeter)

  • Samuel E. Jones

    (University of Exeter Medical School, University of Exeter)

  • Katherine S. Ruth

    (University of Exeter Medical School, University of Exeter)

  • Hanieh Yaghootkar

    (University of Exeter Medical School, University of Exeter)

  • Jessica Tyrrell

    (University of Exeter Medical School, University of Exeter)

  • Aki S. Havulinna

    (National Institute for Health and Welfare)

  • Harmen Boers

    (University of Groningen, University Medical Center Groningen
    University of Groningen, University Medical Center Groningen, Genomics Coordination Center)

  • Reedik Mägi

    (University of Tartu)

  • Jennifer Kriebel

    (German Research Center for Environmental Health
    German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Martina Müller-Nurasyid

    (Helmholtz Zentrum München—German Research Center for Environmental Health
    Ludwig-Maximilians-Universität
    DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance)

  • Markus Perola

    (National Institute for Health and Welfare
    University of Tartu, Estonian Genome Center)

  • Markku Nieminen

    (Heart and Lung Centre HUCH and Helsinki University)

  • Marja-Liisa Lokki

    (Helsinki University)

  • Mika Kähönen

    (Tampere University Hospital
    University of Tampere Faculty of Medicine and Life Sciences)

  • Jorma S. Viikari

    (Turku University Hospital
    University of Turku)

  • Frank Geller

    (Statens Serum Institut)

  • Jari Lahti

    (University of Helsinki
    University of Helsinki)

  • Aarno Palotie

    (University of Helsinki
    The Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Päivikki Koponen

    (National Institute for Health and Welfare)

  • Annamari Lundqvist

    (National Institute for Health and Welfare)

  • Harri Rissanen

    (National Institute for Health and Welfare)

  • Erwin P. Bottinger

    (Icahn School of Medicine at Mount Sinai)

  • Saima Afaq

    (Imperial College London)

  • Mary K. Wojczynski

    (Washington University School of Medicine)

  • Petra Lenzini

    (Washington University School of Medicine)

  • Ilja M. Nolte

    (University of Groningen, University Medical Center Groningen)

  • Thomas Sparsø

    (Mental Health Center Sct. Hans
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Nicole Schupf

    (Columbia University)

  • Kaare Christensen

    (University of Southern Denmark)

  • Thomas T. Perls

    (Boston University, Boston School of Medicine and Boston Medical Center)

  • Anne B. Newman

    (University of Pittsburgh Graduate School of Public Health)

  • Thomas Werge

    (Mental Health Center Sct. Hans
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of Copenhagen)

  • Harold Snieder

    (University of Groningen, University Medical Center Groningen)

  • Timothy D. Spector

    (King’s College London)

  • John C. Chambers

    (Imperial College London
    Ealing Hospital NHS Trust
    Imperial College Healthcare NHS Trust)

  • Seppo Koskinen

    (National Institute for Health and Welfare)

  • Mads Melbye

    (Statens Serum Institut
    University of Copenhagen
    Stanford University School of Medicine)

  • Olli T. Raitakari

    (Turku University Hospital
    University of Turku)

  • Terho Lehtimäki

    (Fimlab Laboratories
    University of Tampere Faculty of Medicine and Life Sciences)

  • Martin D. Tobin

    (University of Leicester
    Glenfield Hospital)

  • Louise V. Wain

    (University of Leicester
    Glenfield Hospital)

  • Juha Sinisalo

    (Heart and Lung Centre HUCH and Helsinki University)

  • Annette Peters

    (German Research Center for Environmental Health
    German Center for Diabetes Research (DZD)
    DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance)

  • Thomas Meitinger

    (Helmholtz Zentrum München
    Technische Universität München)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Institute)

  • Naomi R. Wray

    (University of Queensland)

  • Grant W. Montgomery

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • Sarah E. Medland

    (QIMR Berghofer Medical Research Institute)

  • Morris A. Swertz

    (University of Groningen, University Medical Center Groningen
    University of Groningen, University Medical Center Groningen, Genomics Coordination Center)

  • Erkki Vartiainen

    (National Institute for Health and Welfare)

  • Katja Borodulin

    (National Institute for Health and Welfare)

  • Satu Männistö

    (National Institute for Health and Welfare)

  • Anna Murray

    (University of Exeter Medical School, University of Exeter)

  • Murielle Bochud

    (Lausanne University Hospital)

  • Sébastien Jacquemont

    (Centre Hospitalier Universitaire Sainte Justine
    University Hospital of Lausanne, University of Lausanne)

  • Fernando Rivadeneira

    (Erasmus Medical Center
    Erasmus Medical Center)

  • Thomas F. Hansen

    (Mental Health Center Sct. Hans
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Albertine J. Oldehinkel

    (University of Groningen, University Medical Center Groningen)

  • Massimo Mangino

    (King’s College London
    NIHR Biomedical Research Centre at Guy’s and St Thomas’ Foundation Trust)

  • Michael A. Province

    (Washington University School of Medicine)

  • Panos Deloukas

    (Queen Mary University of London
    King Abdulaziz University)

  • Jaspal S. Kooner

    (Ealing Hospital NHS Trust
    Imperial College Healthcare NHS Trust
    Imperial College London)

  • Rachel M. Freathy

    (University of Exeter Medical School, University of Exeter)

  • Craig Pennell

    (The University of Western Australia)

  • Bjarke Feenstra

    (Statens Serum Institut)

  • David P. Strachan

    (St. George’s, University of London)

  • Guillaume Lettre

    (Université de Montréal
    Université de Montréal)

  • Joel Hirschhorn

    (Broad Institute of MIT and Harvard
    Harvard Medical School
    Harvard Medical School)

  • Daniele Cusi

    (University of Milano
    Italian National Research Council)

  • Iris M. Heid

    (University of Regensburg)

  • Caroline Hayward

    (University of Edinburgh)

  • Katrin Männik

    (University of Tartu
    University of Lausanne)

  • Jacques S. Beckmann

    (Swiss Institute of Bioinformatics)

  • Ruth J. F. Loos

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Dale R. Nyholt

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology)

  • Andres Metspalu

    (University of Tartu)

  • Johan G. Eriksson

    (University of Helsinki and Helsinki University Hospital
    Folkhälsan Research Center)

  • Michael N. Weedon

    (University of Exeter Medical School, University of Exeter)

  • Veikko Salomaa

    (National Institute for Health and Welfare)

  • Lude Franke

    (University of Groningen, University Medical Center Groningen)

  • Alexandre Reymond

    (University of Lausanne)

  • Timothy M. Frayling

    (University of Exeter Medical School, University of Exeter)

  • Zoltán Kutalik

    (Lausanne University Hospital
    Swiss Institute of Bioinformatics)

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/m2). 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/m2 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.

Suggested Citation

  • Aurélien Macé & Marcus A. Tuke & Patrick Deelen & Kati Kristiansson & Hannele Mattsson & Margit Nõukas & Yadav Sapkota & Ursula Schick & Eleonora Porcu & Sina Rüeger & Aaron F. McDaid & David Porteous, 2017. "CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00556-x
    DOI: 10.1038/s41467-017-00556-x
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