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Meta-Analysis
. 2021 Jan;5(1):59-70.
doi: 10.1038/s41562-020-00956-y. Epub 2020 Sep 28.

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

Gabriel Cuellar-Partida  1   2 Joyce Y Tung  2 Nicholas Eriksson  2 Eva Albrecht  3 Fazil Aliev  4   5 Ole A Andreassen  6   7 Inês Barroso  8   9   10 Jacques S Beckmann  11 Marco P Boks  12 Dorret I Boomsma  13   14 Heather A Boyd  15 Monique M B Breteler  16 Harry Campbell  17 Daniel I Chasman  18   19 Lynn F Cherkas  20 Gail Davies  21   22 Eco J C de Geus  13   14 Ian J Deary  21   22 Panos Deloukas  23 Danielle M Dick  4   24 David L Duffy  25 Johan G Eriksson  26   27   28   29 Tõnu Esko  30   31 Bjarke Feenstra  15 Frank Geller  15 Christian Gieger  32   33 Ina Giegling  34 Scott D Gordon  25 Jiali Han  35   36 Thomas F Hansen  37   38 Annette M Hartmann  34 Caroline Hayward  39 Kauko Heikkilä  40 Andrew A Hicks  41 Joel N Hirschhorn  42   43   44 Jouke-Jan Hottenga  13   14 Jennifer E Huffman  39 Liang-Dar Hwang  1 M Arfan Ikram  45 Jaakko Kaprio  40   46 John P Kemp  1   47 Kay-Tee Khaw  48 Norman Klopp  49 Bettina Konte  34 Zoltan Kutalik  50   51 Jari Lahti  52   53   54 Xin Li  35   36 Ruth J F Loos  9   55   56 Michelle Luciano  21   22 Sigurdur H Magnusson  57 Massimo Mangino  20 Pedro Marques-Vidal  58 Nicholas G Martin  25 Wendy L McArdle  59 Mark I McCarthy  60   61   62   63 Carolina Medina-Gomez  45   64 Mads Melbye  15   65   66 Scott A Melville  41 Andres Metspalu  30 Lili Milani  30 Vincent Mooser  67 Mari Nelis  30 Dale R Nyholt  25   68 Kevin S O'Connell  6 Roel A Ophoff  69   70   71 Cameron Palmer  72 Aarno Palotie  40 Teemu Palviainen  40 Guillaume Pare  73 Lavinia Paternoster  74 Leena Peltonen  75 Brenda W J H Penninx  14   76 Ozren Polasek  77   78 Peter P Pramstaller  41 Inga Prokopenko  79   80 Katri Raikkonen  52 Samuli Ripatti  40 Fernando Rivadeneira  45   64 Igor Rudan  81 Dan Rujescu  34 Johannes H Smit  14   76 George Davey Smith  74 Jordan W Smoller  82   83 Nicole Soranzo  8 Tim D Spector  20 Beate St Pourcain  74   84   85 John M Starr  86   87 Hreinn Stefánsson  57 Stacy Steinberg  57 Maris Teder-Laving  30 Gudmar Thorleifsson  57 Kári Stefánsson  57 Nicholas J Timpson  74 André G Uitterlinden  45   64 Cornelia M van Duijn  45   64 Frank J A van Rooij  45 Jaqueline M Vink  13   88 Peter Vollenweider  58 Eero Vuoksimaa  40 Gérard Waeber  58 Nicholas J Wareham  9 Nicole Warrington  1 Dawn Waterworth  89 Thomas Werge  37   65   90 H-Erich Wichmann  91 Elisabeth Widen  40 Gonneke Willemsen  13 Alan F Wright  39 Margaret J Wright  92   93 Mousheng Xu  94 Jing Hua Zhao  95 Peter Kraft  94 David A Hinds  2 Cecilia M Lindgren  60   96 Reedik Mägi  30 Benjamin M Neale  31   97 David M Evans  98   99 Sarah E Medland  100   101
Affiliations
Meta-Analysis

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

Gabriel Cuellar-Partida et al. Nat Hum Behav. 2021 Jan.

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.

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Conflict of interest statement

Competing interests

G.C.-P., N.E., D.A.H. and J.Y.T. are employees of 23andMe, Inc., and hold stock or stock options in 23andMe. S.H.M., K.S., H.S., S.S. and G.T. are employees of deCODE Genetics/Amgen. M.I.M. is a Wellcome Senior Investigator and a NIHR Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. M.I.M. has served on advisory panels for Pfizer, NovoNordisk and Zoe Global; has received honoraria from Merck, Pfizer, NovoNordisk and Eli Lilly; has stock options in Zoe Global; has received research funding from Abbvie, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier and Takeda. As of June 2019, he is an employee of Genentech, and holder of Roche stock. All other authors report no conflicts of interest.

Figures

Fig. 1
Fig. 1. Manhattan plot of the left-handedness meta-analysis.
Manhattan plots for the left-handedness GWAS meta-analysis (N = 1,534,836 right-handed versus 194,198 left-handed). Each dot represents a SNP. The red broken line highlights the genome-wide levels of significance threshold (P < 5 × 10–8); the blue broken line shows the threshold for suggestive associations.
Fig. 2
Fig. 2. Manhattan plot of the ambidexterity meta-analysis.
Manhattan plots for the ambidexterity GWAS meta-analysis (N = 1,422,823 right-handed versus 37,637 ambidextrous individuals). Each dot represents a SNP. The red broken line highlights the genome-wide levels of significance threshold (P < 5 × 10–8); the blue broken line shows the threshold for suggestive associations.

References

    1. Hepper PG, McCartney GR, Shannon EA. Lateralised behaviour in first trimester human foetuses. Neuropsychologia. 1998;36:521–534. - PubMed
    1. Parma V, Brasselet R, Zoia S, Bulgheroni M, Castiello U. The origin of human handedness and its role in pre-birth motor control. Sci Rep. 2017;7 16804. - PMC - PubMed
    1. Lazenby R. Skeletal biology, functional asymmetry and the origins of ‘handedness’. J Theor Biol. 2002;218:129–138. - PubMed
    1. Gumustekin K, et al. Handedness and bilateral femoral bone densities in men and women. Int J Neurosci. 2004;114:1533–1547. - PubMed
    1. Steele J, Mays S. Handedness and directional asymmetry in the long bones of the human upper limb. Int J Osteoarchaeologoy. 1995;5:39–49.

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