Defining the role of common variation in the genomic and biological architecture of adult human height

Andrew R Wood; Tonu Esko; Jian Yang; Sailaja Vedantam; Tune H Pers; Stefan Gustafsson; Audrey Y Chu; Karol Estrada; Jian'an Luan; Zoltán Kutalik; Najaf Amin; Martin L Buchkovich; Damien C Croteau-Chonka; Felix R Day; Yanan Duan; Tove Fall; Rudolf Fehrmann; Teresa Ferreira; Anne U Jackson; Juha Karjalainen; Ken Sin Lo; Adam E Locke; Reedik Mägi; Evelin Mihailov; Eleonora Porcu; Joshua C Randall; André Scherag; Anna A E Vinkhuyzen; Harm-Jan Westra; Thomas W Winkler; Tsegaselassie Workalemahu; Jing Hua Zhao; Devin Absher; Eva Albrecht; Denise Anderson; Jeffrey Baron; Marian Beekman; Ayse Demirkan; Georg B Ehret; Bjarke Feenstra; Mary F Feitosa; Krista Fischer; Ross M Fraser; Anuj Goel; Jian Gong; Anne E Justice; Stavroula Kanoni; Marcus E Kleber; Kati Kristiansson; Unhee Lim; Vaneet Lotay; Julian C Lui; Massimo Mangino; Irene Mateo Leach; Carolina Medina-Gomez; Michael A Nalls; Dale R Nyholt; Cameron D Palmer; Dorota Pasko; Sonali Pechlivanis; Inga Prokopenko; Janina S Ried; Stephan Ripke; Dmitry Shungin; Alena Stancáková; Rona J Strawbridge; Yun Ju Sung; Toshiko Tanaka; Alexander Teumer; Stella Trompet; Sander W van der Laan; Jessica van Setten; Jana V Van Vliet-Ostaptchouk; Zhaoming Wang; Loïc Yengo; Weihua Zhang; Uzma Afzal; Johan Arnlöv; Gillian M Arscott; Stefania Bandinelli; Amy Barrett; Claire Bellis; Amanda J Bennett; Christian Berne; Matthias Blüher; Jennifer L Bolton; Yvonne Böttcher; Heather A Boyd; Marcel Bruinenberg; Brendan M Buckley; Steven Buyske; Ida H Caspersen; Peter S Chines; Robert Clarke; Simone Claudi-Boehm; Matthew Cooper; E Warwick Daw; Pim A De Jong; Joris Deelen; Graciela Delgado; Electronic Medical Records and Genomics (eMEMERGEGE) Consortium

doi:10.1038/ng.3097

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Defining the role of common variation in the genomic and biological architecture of adult human height

Journal article

Peer reviewed

Defining the role of common variation in the genomic and biological architecture of adult human height

Andrew R Wood, Tonu Esko, Jian Yang, Sailaja Vedantam, Tune H Pers, Stefan Gustafsson, Audrey Y Chu, Karol Estrada, Jian'an Luan, Zoltán Kutalik, …

Nature genetics, Vol.46(11), pp.1173-1186

01/11/2014

DOI: https://doi.org/10.1038/ng.3097

PMID: 25282103

Abstract

Adult

Analysis of Variance

Body Height - genetics

Genetic Variation - genetics

Genetics, Population

Genome-Wide Association Study - methods

Humans

Oligonucleotide Array Sequence Analysis

Polymorphism, Single Nucleotide - genetics

Whites - genetics

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

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Title: Defining the role of common variation in the genomic and biological architecture of adult human height
Creators: Andrew R Wood - University of Exeter
Tonu Esko - University of Tartu
Jian Yang - University of Queensland
Sailaja Vedantam - Broad Institute
Tune H Pers - Technical University of Denmark
Stefan Gustafsson - Science for Life Laboratory
Audrey Y Chu - Brigham and Women's Hospital
Karol Estrada - Harvard University
Jian'an Luan - University of Cambridge
Zoltán Kutalik - University of Lausanne
Najaf Amin - Erasmus MC
Martin L Buchkovich - University of North Carolina at Chapel Hill
Damien C Croteau-Chonka - 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Felix R Day - University of Cambridge
Yanan Duan - Washington University in St. Louis
Tove Fall - Science for Life Laboratory
Rudolf Fehrmann - University Medical Center Groningen
Teresa Ferreira - Centre for Human Genetics
Anne U Jackson - University of Michigan–Ann Arbor
Juha Karjalainen - University Medical Center Groningen
Ken Sin Lo - Montreal Heart Institute
Adam E Locke - University of Michigan–Ann Arbor
Reedik Mägi - University of Tartu
Evelin Mihailov - University of Tartu
Eleonora Porcu - Institute of Genetic and Biomedical Research
Joshua C Randall - Centre for Human Genetics
André Scherag - Institut für Medizinische Informatik, Biometrie und Epidemiologie
Anna A E Vinkhuyzen - University of Queensland
Harm-Jan Westra - University of Groningen
Thomas W Winkler - University of Regensburg
Tsegaselassie Workalemahu - Harvard University
Jing Hua Zhao - University of Cambridge
Devin Absher - HudsonAlpha Institute for Biotechnology
Eva Albrecht - Helmholtz Zentrum München
Denise Anderson - The Kids Research Institute Australia
Jeffrey Baron - Eunice Kennedy Shriver National Institute of Child Health and Human Development
Marian Beekman - Leiden University Medical Center
Ayse Demirkan - Erasmus MC
Georg B Ehret - Johns Hopkins University
Bjarke Feenstra - Statens Serum Institut
Mary F Feitosa - Washington University in St. Louis
Krista Fischer - University of Tartu
Ross M Fraser - University of Edinburgh
Anuj Goel - University of Oxford
Jian Gong - Fred Hutch Cancer Center
Anne E Justice - University of North Carolina at Chapel Hill
Stavroula Kanoni - William Harvey Research Institute
Marcus E Kleber - Heidelberg University
Kati Kristiansson - Finnish Institute for Health and Welfare
Unhee Lim - University of Hawaiʻi at Mānoa
Vaneet Lotay - Icahn School of Medicine at Mount Sinai
Julian C Lui - Eunice Kennedy Shriver National Institute of Child Health and Human Development
Massimo Mangino - King's College London
Irene Mateo Leach - University Medical Center Groningen
Carolina Medina-Gomez - Netherlands Consortium for Healthy Ageing
Michael A Nalls - National Institute on Aging
Dale R Nyholt - QIMR Berghofer Medical Research Institute
Cameron D Palmer - Harvard University
Dorota Pasko - University of Exeter
Sonali Pechlivanis - Institut für Medizinische Informatik, Biometrie und Epidemiologie
Inga Prokopenko - Centre for Human Genetics
Janina S Ried - Helmholtz Zentrum München
Stephan Ripke - Massachusetts General Hospital
Dmitry Shungin - Umeå University
Alena Stancáková - University of Eastern Finland
Rona J Strawbridge - Karolinska Institutet
Yun Ju Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA
Toshiko Tanaka - National Institute on Aging
Alexander Teumer - Universitätsmedizin Greifswald
Stella Trompet - Leiden University Medical Center
Sander W van der Laan - University Medical Center Utrecht
Jessica van Setten - University Medical Center Utrecht
Jana V Van Vliet-Ostaptchouk - University Medical Center Groningen
Zhaoming Wang - Universitätsmedizin Greifswald
Loïc Yengo - Université de Lille
Weihua Zhang - Imperial College London
Uzma Afzal - Imperial College London
Johan Arnlöv - Science for Life Laboratory
Gillian M Arscott - Pathwest Laboratory Medicine
Stefania Bandinelli - Azienda Sanitaria di Firenze
Amy Barrett - Oxford Centre for Diabetes, Endocrinology and Metabolism
Claire Bellis - Texas Biomedical Research Institute
Amanda J Bennett - University of Oxford
Christian Berne - Uppsala University
Matthias Blüher - IFB Adiposity Diseases
Jennifer L Bolton - University of Edinburgh
Yvonne Böttcher - IFB Adiposity Diseases
Heather A Boyd - Statens Serum Institut
Marcel Bruinenberg - University of Groningen
Brendan M Buckley - University College Cork
Steven Buyske - Rutgers, The State University of New Jersey
Ida H Caspersen - Norwegian University of Science and Technology
Peter S Chines - National Human Genome Research Institute
Robert Clarke - University of Oxford
Simone Claudi-Boehm - Division of Endocrinology, Diabetes and Metabolism, Ulm University Medical Centre, Ulm, Germany
Matthew Cooper - University of Western Australia
E Warwick Daw - Washington University in St. Louis
Pim A De Jong - University Medical Center Utrecht
Joris Deelen - Leiden University Medical Center
Graciela Delgado - Heidelberg University
Electronic Medical Records and Genomics (eMEMERGEGE) Consortium
Publication Details: Nature genetics, Vol.46(11), pp.1173-1186
Publication Date: 01/11/2014
Grant note: R01 HL087700 / NHLBI NIH HHS MR/L01629X/1 / Medical Research Council R01 DK072193 / NIDDK NIH HHS CZB/4/672 / Chief Scientist Office R01 HL109946 / NHLBI NIH HHS FS/12/33/29561 / British Heart Foundation 090532 / Wellcome Trust P30 CA071789 / NCI NIH HHS P30 HD018655 / NICHD NIH HHS FS/12/8/29377 / British Heart Foundation
Identifiers: 99928801402346; WOS:000344131900008
Academic Unit: School of Biosciences; Institute for Sustainability; Surrey Institute for People-Centred AI
Language: English
Resource Type: Journal article

Defining the role of common variation in the genomic and biological architecture of adult human height

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