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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)59-70
Number of pages12
JournalNature Human Behaviour
Volume5
Issue number1
DOIs
Publication statusPublished - Jan 2021

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