Genome-wide association study identifies 48 common genetic variants associated with handedness

Gabriel Cuéllar-Partida(The University of Queensland), Joyce Y. Tung(23andMe (United States)), Nicholas Eriksson(23andMe (United States)), Eva Albrecht(Helmholtz Zentrum München), Fazil Alıev(Karabük University), Ole A. Andreassen(Oslo University Hospital), Inês Barroso(University of Cambridge), J. Beckmann(University Hospital of Lausanne), Marco P. Boks(University Medical Center Utrecht), Dorret I. Boomsma(Amsterdam University Medical Centers), Heather A. Boyd(Statens Serum Institut), Monique M.B. Breteler(German Center for Neurodegenerative Diseases), Harry Campbell(University of Edinburgh), Daniel I. Chasman(Brigham and Women's Hospital), Lynn Cherkas(King's College London), Gail Davies(University of Edinburgh), Eco J. C. de Geus(Amsterdam University Medical Centers), Ian J. Deary(University of Edinburgh), Panos Deloukas(Queen Mary University of London), Danielle M. Dick(Virginia Commonwealth University), David L. Duffy(QIMR Berghofer Medical Research Institute), Johan G. Eriksson(Agency for Science, Technology and Research), Tōnu Esko(Broad Institute), Bjarke Feenstra(Statens Serum Institut), Frank Geller(Statens Serum Institut), Christian Gieger(Helmholtz Zentrum München), Ina Giegling(Martin Luther University Halle-Wittenberg), Scott D. Gordon(QIMR Berghofer Medical Research Institute), Jiali Han(Indiana University Health), Thomas Folkmann Hansen(Mental Health Services), Annette M. Hartmann(Martin Luther University Halle-Wittenberg), Caroline Hayward(Institute of Genetics and Cancer), Kauko Heikkilä(University of Helsinki), Andrew A. Hicks(Eurac Research), Joel N. Hirschhorn(Broad Institute), Jouke‐Jan Hottenga(Amsterdam University Medical Centers), Jennifer E. Huffman(Institute of Genetics and Cancer), Liang‐Dar Hwang(The University of Queensland), M. Arfan Ikram(Erasmus MC), Jaakko Kaprio(University of Helsinki), John P. Kemp(The University of Queensland), Kay‐Tee Khaw(University of Cambridge), Norman Klopp(Medizinische Hochschule Hannover), Bettina Konte(Martin Luther University Halle-Wittenberg), Zoltán Kutalik(SIB Swiss Institute of Bioinformatics), Jari Lahti(University of Helsinki), Xin Li(Indiana University Health), Ruth J. F. Loos(University of Cambridge), Michelle Luciano(University of Edinburgh), Sigurður H. Magnússon(deCODE Genetics (Iceland)), Massimo Mangino(King's College London), Pedro Marques‐Vidal(University of Lausanne), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Wendy L. McArdle(University of Bristol), Mark I. McCarthy(Centre for Human Genetics), Carolina Medina‐Gómez(Erasmus MC), Mads Melbye(Statens Serum Institut), Scott A. Melville(Eurac Research), Andres Metspalu(University of Tartu), Lili Milani(University of Tartu), Vincent Mooser(University of Lausanne), Mari Nelis(University of Tartu), Dale R. Nyholt(Queensland University of Technology), Kevin S. O’Connell(University of Oslo), Roel A. Ophoff(University of California, Los Angeles), Cameron D. Palmer(Columbia University), Aarno Palotie(University of Helsinki), Teemu Palviainen(University of Helsinki), Guillaume Paré(McMaster University), Lavinia Paternoster(University of Bristol), Leena Peltonen(University of Helsinki), Brenda W.J.H. Penninx(Amsterdam University Medical Centers), Ozren Polašek(Psychiatric Hospital Sveti Ivan), Peter P. Pramstaller(Eurac Research), Inga Prokopenko(University of Surrey), Katri Räikkönen(University of Helsinki), Samuli Ripatti(University of Helsinki), Fernando Rivadeneira(Erasmus MC), Igor Rudan(University of Edinburgh), Dan Rujescu(Martin Luther University Halle-Wittenberg), Johannes H. Smit(Amsterdam University Medical Centers), George Davey Smith(University of Bristol), Jordan W. Smoller(Broad Institute), Nicole Soranzo(Wellcome Sanger Institute), Tim D. Spector(King's College London), Beaté St Pourcain(Radboud University Nijmegen), John M. Starr(Alzheimer Scotland), Hreinn Stefánsson(deCODE Genetics (Iceland)), Stacy Steinberg(deCODE Genetics (Iceland)), Maris Teder‐Laving(University of Tartu), Guðmar Þorleifsson(deCODE Genetics (Iceland)), Kāri Stefánsson(deCODE Genetics (Iceland)), Nicholas J. Timpson(University of Bristol), André G. Uitterlinden(Erasmus MC), Cornelia M. van Duijn(Erasmus MC), Frank J.A. van Rooij(Erasmus MC), Jaqueline M. Vink(Radboud University Nijmegen), Péter Vollenweider(University of Lausanne), Eero Vuoksimaa(University of Helsinki), Gérard Waeber(University of Lausanne), Nicholas J. Wareham(University of Cambridge), Nicole M. Warrington(The University of Queensland), Dawn Waterworth(GlaxoSmithKline (United States)), Thomas Werge(University of Copenhagen), H.‐Erich Wichmann(Helmholtz Zentrum München), Elisabeth Widén(University of Helsinki), Gonneke Willemsen(Vrije Universiteit Amsterdam), Alan F. Wright(Institute of Genetics and Cancer), Margaret J. Wright(The University of Queensland), Mousheng Xu(Harvard University), Jing Hua Zhao(University of Cambridge), Peter Kraft(Harvard University), David A. Hinds(23andMe (United States)), Cecilia M. Lindgren(Centre for Human Genetics), Reedik Mägi(University of Tartu), Benjamin M. Neale(Broad Institute), David M. Evans(The University of Queensland), Sarah E. Medland(The University of Queensland)
Nature Human Behaviour
September 28, 2020
10.1038/s41562-020-00956-y
Cited by 156Open Access
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Abstract

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders. A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.

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