A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Janina S. Ried; Janina M. Jeff; Audrey Y. Chu; Jennifer L. Bragg-Gresham; Jenny van Dongen; Jennifer E. Huffman; Tarunveer S. Ahluwalia; Gemma Cadby; Niina Eklund; Joel Eriksson; Tonu Esko; Mary F. Feitosa; Anuj Goel; Mathias Gorski; Caroline Hayward; Nancy L. Heard-Costa; Anne U. Jackson; Eero Jokinen; Stavroula Kanoni; Kati Kristiansson; Zoltan Kutalik; Jari Lahti; Jian'an Luan; Reedik Maegi; Anubha Mahajan; Massimo Mangino; Carolina Medina-Gomez; Keri L. Monda; Ilja M. Nolte; Louis Perusse; Inga Prokopenko; Lu Qi; Lynda M. Rose; Erika Salvi; Megan T. Smith; Harold Snieder; Alena Stancakova; Yun Ju Sung; Ioanna Tachmazidou; Alexander Teumer; Gudmar Thorleifsson; Pim van der Harst; Ryan W. Walker; Sophie R. Wang; Sarah H. Wild; Sara M. Willems; Andrew Wong; Weihua Zhang; Eva Albrecht; Alexessander Couto Alves; Stephan J. L. Bakker; Cristina Barlassina; Traci M. Bartz; John Beilby; Claire Bellis; Richard N. Bergman; Sven Bergmann; John Blangero; Matthias Blueher; Eric Boerwinkle; Lori L. Bonnycastle; Stefan R. Bornstein; Marcel Bruinenberg; Harry Campbell; Yii-Der Ida Chen; Charleston W. K. Chiang; Peter S. Chines; Francis S. Collins; Fracensco Cucca; L. Adrienne Cupples; Francesca D'Avila; Eco J. C. de Geus; George Dedoussis; Maria Dimitriou; Angela Doering; Johan G. Eriksson; Aliki-Eleni Farmaki; Martin Farrall; Teresa Ferreira; Krista Fischer; Nita G. Forouhi; Nele Friedrich; Anette Prior Gjesing; Nicola Glorioso; Mariaelisa Graff; Harald Grallert; Niels Grarup; Juergen Graessler; Jagvir Grewal; Anders Hamsten; Marie Neergaard Harder; Catharina A. Hartman; Maija Hassinen; Nicholas Hastie; Andrew Tym Hattersley; Aki S. Havulinna; Markku Heliovaara; Hans Hillege; Albert Hofman; Oddgeir Holmen

doi:10.1038/ncomms13357

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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Janina S. Ried, Janina M. Jeff, Audrey Y. Chu, Jennifer L. Bragg-Gresham, Jenny van Dongen, Jennifer E. Huffman, Tarunveer S. Ahluwalia, Gemma Cadby, Niina Eklund, Joel Eriksson, …

Nature communications, Vol.7(1), pp.13357-13357

23/11/2016

DOI: https://doi.org/10.1038/ncomms13357

PMID: 27876822

Abstract

Multidisciplinary Sciences

Science & Technology

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Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

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Title: A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
Creators: Janina S. Ried - Helmholtz Zentrum München
Janina M. Jeff - Supreme Council Of Health
Audrey Y. Chu - Brigham and Women's Hospital
Jennifer L. Bragg-Gresham - College Station Medical Center
Jenny van Dongen - University of Amsterdam
Jennifer E. Huffman - University of Edinburgh
Tarunveer S. Ahluwalia - University of Copenhagen
Gemma Cadby - University of Western Australia
Niina Eklund - Finnish Institute for Health and Welfare
Joel Eriksson - University of Gothenburg
Tonu Esko - Broad Institute
Mary F. Feitosa - Washington University in St. Louis
Anuj Goel - University of Oxford
Mathias Gorski - University Hospital Regensburg
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Nancy L. Heard-Costa - Framingham Heart Study
Anne U. Jackson - University of Michigan–Ann Arbor
Eero Jokinen - University of Helsinki
Stavroula Kanoni - Wellcome Sanger Institute
Kati Kristiansson - Finnish Institute for Health and Welfare
Zoltan Kutalik - SIB Swiss Institute of Bioinformatics
Jari Lahti - Folkhälsans Forskningscentrum
Jian'an Luan - University of Cambridge
Reedik Maegi - University of Tartu
Anubha Mahajan - University of Oxford
Massimo Mangino - King's College London
Carolina Medina-Gomez - Erasmus MC
Keri L. Monda - University of North Carolina at Chapel Hill
Ilja M. Nolte - University Medical Center Groningen
Louis Perusse - Université Laval
Inga Prokopenko - Wellcome Centre for Human Genetics
Lu Qi - Brigham and Women's Hospital
Lynda M. Rose - Brigham and Women's Hospital
Erika Salvi - Ospedale San Paolo
Megan T. Smith - University of Washington
Harold Snieder - University Medical Center Groningen
Alena Stancakova - Kuopio University Hospital
Yun Ju Sung - Biostat
Ioanna Tachmazidou - Wellcome Sanger Institute
Alexander Teumer - Universitätsmedizin Greifswald
Gudmar Thorleifsson - Amgen
Pim van der Harst - Netherlands Heart Institute
Ryan W. Walker - Icahn School of Medicine at Mount Sinai
Sophie R. Wang - Harvard University
Sarah H. Wild - University of Edinburgh
Sara M. Willems - Erasmus MC
Andrew Wong - MRC Unit for Lifelong Health and Ageing
Weihua Zhang - Imperial College London
Eva Albrecht - Helmholtz Zentrum München
Alexessander Couto Alves - Imperial College London
Stephan J. L. Bakker - University Medical Center Groningen
Cristina Barlassina - Ospedale San Paolo
Traci M. Bartz - University of Washington
John Beilby - Pathwest Laboratory Medicine
Claire Bellis - Queensland University of Technology
Richard N. Bergman - Cedars-Sinai Medical Center
Sven Bergmann - SIB Swiss Institute of Bioinformatics
John Blangero - The University of Texas Rio Grande Valley
Matthias Blueher - Institute of Inland Fisheries in Potsdam-Sacrow
Eric Boerwinkle - The University of Texas Health Science Center at Houston
Lori L. Bonnycastle - National Human Genome Research Institute
Stefan R. Bornstein - University Hospital Carl Gustav Carus
Marcel Bruinenberg - University Medical Center Groningen
Harry Campbell - University of Edinburgh
Yii-Der Ida Chen - Harbor–UCLA Medical Center
Charleston W. K. Chiang - University of California, Los Angeles
Peter S. Chines - National Human Genome Research Institute
Francis S. Collins - National Human Genome Research Institute
Fracensco Cucca - University of Sassari
L. Adrienne Cupples - Framingham Heart Study
Francesca D'Avila - University of Milan
Eco J. C. de Geus - University of Amsterdam
George Dedoussis - Harokopio University of Athens
Maria Dimitriou - Wellcome Sanger Institute
Angela Doering - Helmholtz Zentrum München
Johan G. Eriksson - Folkhälsans Forskningscentrum
Aliki-Eleni Farmaki - Harokopio University of Athens
Martin Farrall - University of Oxford
Teresa Ferreira - Wellcome Centre for Human Genetics
Krista Fischer - University of Tartu
Nita G. Forouhi - MRC Epidemiology Unit
Nele Friedrich - Universitätsmedizin Greifswald
Anette Prior Gjesing - University of Copenhagen
Nicola Glorioso - University of Sassari
Mariaelisa Graff - University of North Carolina at Chapel Hill
Harald Grallert - Helmholtz Zentrum München
Niels Grarup - Novo Nordisk Foundation
Juergen Graessler - College Station Medical Center
Jagvir Grewal - Imperial College London
Anders Hamsten - Karolinska Institutet
Marie Neergaard Harder - Novo Nordisk Foundation
Catharina A. Hartman - University Medical Center Groningen
Maija Hassinen - University of Eastern Finland
Nicholas Hastie - MRC Institute of Genetics and Molecular Medicine
Andrew Tym Hattersley - University of Exeter
Aki S. Havulinna - Finnish Institute for Health and Welfare
Markku Heliovaara - Finnish Institute for Health and Welfare
Hans Hillege - University Medical Center Groningen
Albert Hofman - Erasmus MC
Oddgeir Holmen - Norwegian University of Science and Technology
Publication Details: Nature communications, Vol.7(1), pp.13357-13357
Publisher: Springer Nature
Number of pages: 11
Date published: 23/11/2016
Grant note: R01HL117626 / 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) P2CHD050924 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) U01DK062370 / 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) 098395 / Wellcome Trust; European Commission UL1 TR000124 / NCATS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) MC_U106179472 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission CL-2011-18-004 / National Institute for Health Research; National Institute for Health Research (NIHR) MC_PC_U127561128 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NF-SI-0611-10219 / Department of Health; European Commission
Identifiers: 99928699702346
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

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