Genome-wide association study identifies 48 common genetic variants associated with handedness
Authors: Partida Gabriel Cuellar , Tung Joyce Y , Eriksson Nicholas , Albrecht Eva , Aliev Fazil , Andreassen Ole A , Barroso Inês , Beckmann Jacques S , Boks Marco P , Boomsma Dorret I , Boyd Heather A , Breteler Monique MB , Campbell Harry , Chasman Daniel I , Cherkas Lynn F , Davies Gail , de Geus Eco JC , Deary Ian J , Deloukas Panos , Dick Danielle M , Duffy David L , Eriksson Johan G , Esko Tõnu , Feenstra Bjarke , Geller Frank , Gieger Christian , Giegling Ina , Gordon Scott D , Han Jiali , Hansen Thomas F , Hartmann Annette M , Hayward Caroline , Heikkilä Kauko , Hicks Andrew A , Hirschhorn Joel N , Hottenga Jouke-Jan , Huffman Jennifer E , Hwang Liang-Dar , Ikram Mohammad A , Kaprio Jaakko , Kemp John P , Khaw Kay-Tee , Klopp Norman , Konte Bettina , Kutalik Zoltan , Lahti Jari , Li Xin , Loos Ruth JF , Luciano Michelle , Magnusson Sigurdur H , Mangino Massimo , Marques-Vidal Pedro , Martin Nicholas G , McArdle Wendy L , McCarthy Mark I , Medina-Gomez Carolina , Melbye Mads , Melville Scott A , Metspalu Andres , Milani Lili , Mooser Vincent , Nelis Mari , Nyholt Dale R , O’Connell Kevin S , Ophoff Roel A , Palmer Cameron , Palotie Aarno , Palviainen Teemu , Pare Guillaume , Paternoster Lavinia , Peltonen Leena , Penninx Brenda WJH , Polasek Ozren , Pramstaller Peter P , Prokopenko Inga , Raikkonen Katri , Ripatti Samuli , Rivadeneira Fernando , Rudan Igor , Rujescu Dan , Smit Johannes H , Smith George Davey , Smoller Jordan W , Soranzo Nicole , Spector Tim D , St Pourcain Beate , Starr John M , Stefánsson Hreinn , Steinberg Stacy , Teder-Laving Maris , Thorleifsson Gudmar , Stefansson Kari , Timpson Nicholas J , Uitterlinden André G , van Duijn Cornelia M , van Rooij Frank JA , Vink Jaqueline M , Vollenweider Peter , Vuoksimaa Eero , Waeber Gérard , Wareham Nicholas J , Warrington Nicole , Waterworth Dawn , Werge Thomas , Wichmann H.-Erich , Widen Elisabeth , Willemsen Gonneke , Wright Alan F , Wright Margaret J , Xu Mousheng , Zhao Jing Hua , Kraft Peter , Hinds David A , Lindgren Cecilia M , Magi Reedik , Neale Benjamin M , Evans David M , Medland Sarah E 
Published: November 2019

Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively 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 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.