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

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; Thomas W Winkler; Erika Salvi; Nick Shrine; Xueping Liu; Wei Q Ang; Weihua Zhang; Mary F Feitosa; Cristina Venturini; Peter J van der Most; Anders Rosengren; Andrew R Wood; Robin N Beaumont; Samuel E Jones; Katherine S Ruth; Hanieh Yaghootkar; Jessica Tyrrell; Aki S Havulinna; Harmen Boers; Reedik Mägi; Jennifer Kriebel; Martina Müller-Nurasyid; Markus Perola; Markku Nieminen; Marja-Liisa Lokki; Mika Kähönen; Jorma S Viikari; Frank Geller; Jari Lahti; Aarno Palotie; Päivikki Koponen; Annamari Lundqvist; Harri Rissanen; Erwin P Bottinger; Saima Afaq; Mary K Wojczynski; Petra Lenzini; Ilja M Nolte; Thomas Sparsø; Nicole Schupf; Kaare Christensen; Thomas T Perls; Anne B Newman; Thomas Werge; Harold Snieder; Timothy D Spector; John C Chambers; Seppo Koskinen; Mads Melbye; Olli T Raitakari; Terho Lehtimäki; Martin D Tobin; Louise V Wain; Juha Sinisalo; Annette Peters; Thomas Meitinger; Nicholas G Martin; Naomi R Wray; Grant W Montgomery; Sarah E Medland; Morris A Swertz; Erkki Vartiainen; Katja Borodulin; Satu Männistö; Anna Murray; Murielle Bochud; Sébastien Jacquemont; Fernando Rivadeneira; Thomas F Hansen; Albertine J Oldehinkel; Massimo Mangino; Michael A Province; Panos Deloukas; Jaspal S Kooner; Rachel M Freathy; Craig Pennell; Bjarke Feenstra; David P Strachan; Guillaume Lettre; Joel Hirschhorn; Daniele Cusi; Iris M Heid; Caroline Hayward; Katrin Männik; Jacques S Beckmann; Ruth J F Loos; Dale R Nyholt; Andres Metspalu; Johan G Eriksson; Michael N Weedon; Veikko Salomaa; Lude Franke; Alexandre Reymond; Timothy M Frayling; Zoltán Kutalik

doi:10.1038/s41467-017-00556-x

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

Journal article

Open access

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

Aurélien Macé, Marcus A Tuke, Patrick Deelen, Kati Kristiansson, Hannele Mattsson, Margit Nõukas, Yadav Sapkota, Ursula Schick, Eleonora Porcu, Sina Rüeger, …

Nature communications, Vol.8(1), pp.744-11

29/09/2017

DOI: https://doi.org/10.1038/s41467-017-00556-x

PMCID: PMC5622064

PMID: 28963451

Abstract

Anthropometry

Body Height - genetics

Body Mass Index

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

Genome-Wide Association Study

Genotype

Humans

Phenotype

Waist-Hip Ratio

Whites - genetics

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.

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Title: CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits
Creators - without role: Aurélien Macé - Institute of Social and Preventive Medicine
Marcus A Tuke - University of Exeter
Patrick Deelen - University Medical Center Groningen
Kati Kristiansson - Finnish Institute for Health and Welfare
Hannele Mattsson - Finnish Institute for Health and Welfare
Margit Nõukas - University of Tartu
Yadav Sapkota - St. Jude Children's Research Hospital
Ursula Schick - Icahn School of Medicine at Mount Sinai
Eleonora Porcu - SIB Swiss Institute of Bioinformatics
Sina Rüeger - Institute of Social and Preventive Medicine
Aaron F McDaid - Institute of Social and Preventive Medicine
David 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 Q Ang - University of Western Australia
Weihua Zhang - Imperial College London
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 - DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, 80336, Germany
Markus Perola - Finnish Institute for Health and Welfare
Markku Nieminen - University of Helsinki
Marja-Liisa Lokki - University of Helsinki
Mika Kähönen - Tampere University
Jorma S Viikari - University of Turku
Frank Geller - Statens Serum Institut
Jari Lahti - University of Helsinki
Aarno Palotie - Massachusetts General Hospital
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 Bottinger - 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 - Lundbeck Foundation
Harold Snieder - University of Groningen
Timothy D Spector - King's College London
John C Chambers - Ealing Hospital
Seppo Koskinen - Finnish Institute for Health and Welfare
Mads Melbye - University of Copenhagen
Olli T Raitakari - Turku University Hospital
Terho Lehtimäki - Tampere University
Martin D Tobin - Glenfield Hospital
Louise V Wain - Glenfield Hospital
Juha Sinisalo - University of Helsinki
Annette Peters - Helmholtz Zentrum München
Thomas Meitinger - Helmholtz Zentrum München
Nicholas G Martin - QIMR Berghofer Medical Research Institute
Naomi R Wray - University of Queensland
Grant W Montgomery - QIMR Berghofer Medical Research Institute
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 F Hansen - Lundbeck Foundation
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 London
Rachel M Freathy - University of Exeter
Craig Pennell - University of Western Australia
Bjarke Feenstra - Statens Serum Institut
David P Strachan - St George's, University of London
Guillaume Lettre - Université de Montréal
Joel Hirschhorn - Broad Institute
Daniele Cusi - University of Milan
Iris M Heid - University of Regensburg
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Katrin Männik - University of Tartu
Jacques S 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 - National Institute for Health and Welfare, Helsinki, 00271, Finland
Lude Franke - University Medical Center Groningen
Alexandre Reymond - University of Lausanne
Timothy M Frayling - University of Exeter
Zoltán Kutalik - SIB Swiss Institute of Bioinformatics
Publication Details: Nature communications, Vol.8(1), pp.744-11
Grant note: U01 AG023755 / NIA NIH HHS Wellcome Trust MR/N011317/1 / Medical Research Council S10 OD018522 / NIH HHS MR/N01104X/1 / Medical Research Council G1001799 / Medical Research Council MR/N01104X/2 / Medical Research Council U01 AG023749 / NIA NIH HHS R01 HL117078 / NHLBI NIH HHS MC_PC_U127561128 / Medical Research Council 323195 / European Research Council G0902313 / Medical Research Council U01 AG023746 / NIA NIH HHS
Identifiers: 9936486208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article