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 x 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 (r(G) = 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.
GrantsResearch Institute for Diseases in the Elderly Neuroscience Campus Amsterdam (NCA) Amsterdam Public Health (APH) KNAW Academy Professor Award Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL) NWO Netherlands Organization for Scientific research (NWO) Wellcome Trust Oak Foundation NHMRC Senior Research Fellowship European Community 7th Framework Program (FP7/2007-2013): ENGAGE European Community 7th Framework Program (FP7/2007-2013): ACTION Genetic Laboratory of the Department of Internal Medicine, Erasmus MC Netherlands Organisation of Scientific Research NWO Investments Developmental Trajectories of Psychopathology Grand Opportunity grants Integration of Genomics and Transcriptomics Determinants of Adolescent Exercise Behavior Major depression: stage 1 genome-wide association in population-based samples Developmental Study of Attention Problems in Young Twins (NIMH) Collaborative Study of the Genetics of DZ twinning Rutgers University Cell and DNA Repository cooperative agreement Australian National Health and Medical Research Council Early Career Fellowship NIHR Widenlife NIHR Biomedical Research Centre, Oxford WT-SSI/John Fell funds Li Ka Shing Foundation Australia Research Council Discovery Early Career Researcher Award National Health and Medical Research Council Senior Research Fellowship NIH Estonian Research Council Wellcome Institute of Genomics, University of Tartu University of Queensland Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) UK Medical Research Council ENGAGE -European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007 Broad Institute Wellcome Trust Sanger Institute Danish Medical Research Council Lundbeck Foundation Health Foundation Augustinus Foundation National Institute of Alcohol Abuse and Alcoholism Academy of Finland March of Dimes Birth Defects Foundation Egmont Foundation Novo Nordisk Foundation Folkhalsan Research Foundation Finnish Diabetes Research Society Municipality of Rotterdam European Commission (DG XII) Ministry for Health, Welfare and Sports Ministry of Education, Culture and Science Research Institute for Diseases in the Elderly (RIDE) Netherlands Organization for the Health Research and Development (ZonMw) Erasmus University, Rotterdam Finska Lakaresallskapet Juho Vainio Foundation Pharmacy Foundation Danish National Research Foundation Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, as part of LMUinnovativ State of Bavaria Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF) Emil Aaltonen Foundation Ahokas Foundation Ministry of Education University of Helsinki Signe and Ane Gyllenberg Foundation Erasmus Medical Center, Rotterdam