Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
28963451
TITLE
CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits.
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 ). 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 for each Mb of total deletion burden (P = 2.5 × 10 , 6.0 × 10 , and 2.9 × 10 ). 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.Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.
DATE PUBLISHED
2017 09 29
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/02/28
accepted 2017/07/10
entrez 2017/10/01 06:00
pubmed 2017/10/01 06:00
medline 2018/01/27 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Macé A Macé Aurélien A Department of Computational Biology, University of Lausanne, Lausanne, 1011, Switzerland.
Tuke MA Tuke Marcus A MA Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Deelen P Deelen Patrick P University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, 9713 GZ, The Netherlands.
Kristiansson K Kristiansson Kati K Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, FI-00014, Finland.
Mattsson H Mattsson Hannele H Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, FI-00014, Finland.
Nõukas M Nõukas Margit M Institute of Molecular and Cell Biology, University of Tartu, Tartu, 51010, Estonia.
Sapkota Y Sapkota Yadav Y St. Jude Children's Research hospital, Memphis, TN, 38105, USA.
Schick U Schick Ursula U The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Porcu E Porcu Eleonora E Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland.
Rüeger S Rüeger Sina S Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
McDaid AF McDaid Aaron F AF Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
Porteous D Porteous David D Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Winkler TW Winkler Thomas W TW Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93053, Germany.
Salvi E Salvi Erika E Department of Health Sciences, University of Milano, Milano, 20090, Italy.
Shrine N Shrine Nick N Department of Health Sciences, University of Leicester, Leicester, LE1 7RH, UK.
Liu X Liu Xueping X Department of Epidemiology Research, Statens Serum Institut, Copenhagen, 2300, Denmark.
Ang WQ Ang Wei Q WQ School of Women's and Infants' Health, The University of Western Australia, Perth, 6009, Australia.
Zhang W Zhang Weihua W Department of Cardiology, Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex, UB1 3EU, UK.
Feitosa MF Feitosa Mary F MF Department of Genetics, Washington University School of Medicine, St. Louis, 63108, USA.
Venturini C Venturini Cristina C Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
van der Most PJ van der Most Peter J PJ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Rosengren A Rosengren Anders A iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, 8210, Denmark.
Wood AR Wood Andrew R AR Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Beaumont RN Beaumont Robin N RN Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Jones SE Jones Samuel E SE Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Ruth KS Ruth Katherine S KS Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Yaghootkar H Yaghootkar Hanieh H Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Tyrrell J Tyrrell Jessica J Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Havulinna AS Havulinna Aki S AS National Institute for Health and Welfare, Helsinki, 00271, Finland.
Boers H Boers Harmen H University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, 9713 GZ, The Netherlands.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Kriebel J Kriebel Jennifer J German Center for Diabetes Research (DZD), Muenchen-Neuherberg, 85764, Germany.
Müller-Nurasyid M Müller-Nurasyid Martina M DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, 80336, Germany.
Perola M Perola Markus M University of Tartu, Estonian Genome Center, Tartu, 51010, Estonia.
Nieminen M Nieminen Markku M Heart and Lung Centre HUCH and Helsinki University, Helsinki, 00029, Finland.
Lokki ML Lokki Marja-Liisa ML Medicum, Helsinki University, Helsinki, 00014, Finland.
Kähönen M Kähönen Mika M Department of Clinical Physiology, University of Tampere Faculty of Medicine and Life Sciences, Tampere, 33521, Finland.
Viikari JS Viikari Jorma S JS Department of Medicine, University of Turku, Turku, 20521, Finland.
Geller F Geller Frank F Department of Epidemiology Research, Statens Serum Institut, Copenhagen, 2300, Denmark.
Lahti J Lahti Jari J Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00014, Finland.
Palotie A Palotie Aarno A Analytic and Translational Genetics Unit, Department of Medicine and Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
Koponen P Koponen Päivikki P National Institute for Health and Welfare, Helsinki, 00271, Finland.
Lundqvist A Lundqvist Annamari A National Institute for Health and Welfare, Helsinki, 00271, Finland.
Rissanen H Rissanen Harri H National Institute for Health and Welfare, Helsinki, 00271, Finland.
Bottinger EP Bottinger Erwin P EP The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Afaq S Afaq Saima S Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK.
Wojczynski MK Wojczynski Mary K MK Department of Genetics, Washington University School of Medicine, St. Louis, 63108, USA.
Lenzini P Lenzini Petra P Department of Genetics, Washington University School of Medicine, St. Louis, 63108, USA.
Nolte IM Nolte Ilja M IM Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Sparsø T Sparsø Thomas T iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, 8210, Denmark.
Schupf N Schupf Nicole N Taub Institute, College of Physicians and Surgeons, Columbia University, New York, NY, 10032, USA.
Christensen K Christensen Kaare K The Danish Aging Research Center, Epidemiology, University of Southern Denmark, Odense, 5000, Denmark.
Perls TT Perls Thomas T TT Section of Geriatrics, Department of Medicine, Boston University, Boston School of Medicine and Boston Medical Center, Boston, MA, 02118, USA.
Newman AB Newman Anne B AB Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, 15261, USA.
Werge T Werge Thomas T Institute of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Spector TD Spector Timothy D TD Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK.
Chambers JC Chambers John C JC Imperial College Healthcare NHS Trust, London, W12 0HS, UK.
Koskinen S Koskinen Seppo S National Institute for Health and Welfare, Helsinki, 00271, Finland.
Melbye M Melbye Mads M Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Raitakari OT Raitakari Olli T OT Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20521, Finland.
Lehtimäki T Lehtimäki Terho T Department of Clinical Chemistry, University of Tampere Faculty of Medicine and Life Sciences, Tampere, 33521, Finland.
Tobin MD Tobin Martin D MD National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK.
Wain LV Wain Louise V LV National Institute for Health Research, Leicester Respiratory Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK.
Sinisalo J Sinisalo Juha J Heart and Lung Centre HUCH and Helsinki University, Helsinki, 00029, Finland.
Peters A Peters Annette A DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, 80336, Germany.
Meitinger T Meitinger Thomas T Institute of Human Genetics, Technische Universität München, Munich, 81675, Germany.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.
Wray NR Wray Naomi R NR Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia.
Montgomery GW Montgomery Grant W GW The Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, 4072, Australia.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, 4006, Australia.
Swertz MA Swertz Morris A MA University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, 9713 GZ, The Netherlands.
Vartiainen E Vartiainen Erkki E National Institute for Health and Welfare, Helsinki, 00271, Finland.
Borodulin K Borodulin Katja K National Institute for Health and Welfare, Helsinki, 00271, Finland.
Männistö S Männistö Satu S National Institute for Health and Welfare, Helsinki, 00271, Finland.
Murray A Murray Anna A Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Bochud M Bochud Murielle M Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, 1010, Switzerland.
Jacquemont S Jacquemont Sébastien S Service of Medical Genetics, University Hospital of Lausanne, University of Lausanne, Lausanne, 1011, Switzerland.
Rivadeneira F Rivadeneira Fernando F Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands.
Hansen TF Hansen Thomas F TF iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, 8210, Denmark.
Oldehinkel AJ Oldehinkel Albertine J AJ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Mangino M Mangino Massimo M NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, SE1 9RT, UK.
Province MA Province Michael A MA Department of Genetics, Washington University School of Medicine, St. Louis, 63108, USA.
Deloukas P Deloukas Panos P Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, 21589, Saudi Arabia.
Kooner JS Kooner Jaspal S JS National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London, W12 0NN, UK.
Freathy RM Freathy Rachel M RM Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Pennell C Pennell Craig C School of Women's and Infants' Health, The University of Western Australia, Perth, 6009, Australia.
Feenstra B Feenstra Bjarke B Department of Epidemiology Research, Statens Serum Institut, Copenhagen, 2300, Denmark.
Strachan DP Strachan David P DP Population Health Research Institute, St. George's, University of London, London, SW17 0RE, UK.
Lettre G Lettre Guillaume G Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada, H3T 1J4.
Hirschhorn J Hirschhorn Joel J Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Cusi D Cusi Daniele D Institute of Biomedical Technologies, Italian National Research Council, Milano, 20090, Italy.
Heid IM Heid Iris M IM Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93053, Germany.
Hayward C Hayward Caroline C Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Männik K Männik Katrin K Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland.
Beckmann JS Beckmann Jacques S JS Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
Loos RJF Loos Ruth J F RJF The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, 10029, USA.
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 4059, Australia.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
Eriksson JG Eriksson Johan G JG Folkhälsan Research Center, Helsinki, 00250, Finland.
Weedon MN Weedon Michael N MN Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Salomaa V Salomaa Veikko V National Institute for Health and Welfare, Helsinki, 00271, Finland.
Franke L Franke Lude L Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands.
Reymond A Reymond Alexandre A Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland.
Frayling TM Frayling Timothy M TM Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Kutalik Z Kutalik Zoltán Z Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland. zoltan.kutalik@unil.ch.
INVESTIGATORS
JOURNAL
VOLUME: 8
ISSUE: 1
TITLE: Nature communications
ISOABBREVIATION: Nat Commun
YEAR: 2017
MONTH: 09
DAY: 29
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2041-1723
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Commun
COUNTRY: England
ISSNLINKING: 2041-1723
NLMUNIQUEID: 101528555
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
G1001799 Medical Research Council United Kingdom
MR/N01104X/2 Medical Research Council United Kingdom
MR/N011317/1 Medical Research Council United Kingdom
S10 OD018522 NIH HHS United States
MR/N01104X/1 Medical Research Council United Kingdom
U01 AG023749 NIA NIH HHS United States
U01 AG023755 NIA NIH HHS United States
G0902313 Medical Research Council United Kingdom
U01 AG023746 NIA NIH HHS United States
R01 HL117078 NHLBI NIH HHS United States
Wellcome Trust United Kingdom
323195 European Research Council International
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Anthropometry
Body Height genetics
Body Mass Index genetics
Body Size genetics
Body Weight genetics
Chromosomes, Human, Pair 1 genetics
Chromosomes, Human, Pair 11 genetics
Chromosomes, Human, Pair 16 genetics
Chromosomes, Human, Pair 18 genetics
Chromosomes, Human, Pair 22 genetics
Chromosomes, Human, Pair 3 genetics
Chromosomes, Human, Pair 7 genetics
DNA Copy Number Variations genetics
European Continental Ancestry Group genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Phenotype genetics
Waist-Hip Ratio genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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