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

doi:10.1038/s41562-020-00956-y

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 Tung², Nicholas Eriksson², Eva Albrecht³, Fazil Aliev^{4

5}, Ole A Andreassen^{6

7}, Inês Barroso^{8

9

10}, Jacques S Beckmann¹¹, Marco P Boks¹², Dorret I Boomsma^{13

14}, Heather A Boyd¹⁵, Monique M B Breteler¹⁶, Harry Campbell¹⁷, Daniel I Chasman^{18

19}, Lynn F Cherkas²⁰, Gail Davies^{21

22}, Eco J C de Geus^{13

14}, Ian J Deary^{21

22}, Panos Deloukas²³, Danielle M Dick^{4

24}, David L Duffy²⁵, Johan G Eriksson^{26

27

28

29}, Tõnu Esko^{30

31}, Bjarke Feenstra¹⁵, Frank Geller¹⁵, Christian Gieger^{32

33}, Ina Giegling³⁴, Scott D Gordon²⁵, Jiali Han^{35

36}, Thomas F Hansen^{37

38}, Annette M Hartmann³⁴, Caroline Hayward³⁹, Kauko Heikkilä⁴⁰, Andrew A Hicks⁴¹, Joel N Hirschhorn^{42

43

44}, Jouke-Jan Hottenga^{13

14}, Jennifer E Huffman³⁹, Liang-Dar Hwang¹, M Arfan Ikram⁴⁵, Jaakko Kaprio^{40

46}, John P Kemp^{1

47}, Kay-Tee Khaw⁴⁸, Norman Klopp⁴⁹, Bettina Konte³⁴, 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 Magnusson⁵⁷, Massimo Mangino²⁰, Pedro Marques-Vidal⁵⁸, Nicholas G Martin²⁵, Wendy L McArdle⁵⁹, Mark I McCarthy^{60

61

62

63}, Carolina Medina-Gomez^{45

64}, Mads Melbye^{15

65

66}, Scott A Melville⁴¹, Andres Metspalu³⁰, Lili Milani³⁰, Vincent Mooser⁶⁷, Mari Nelis³⁰, Dale R Nyholt^{25

68}, Kevin S O'Connell⁶, Roel A Ophoff^{69

70

71}, Cameron Palmer⁷², Aarno Palotie⁴⁰, Teemu Palviainen⁴⁰, Guillaume Pare⁷³, Lavinia Paternoster⁷⁴, Leena Peltonen⁷⁵, Brenda W J H Penninx^{14

76}, Ozren Polasek^{77

78}, Peter P Pramstaller⁴¹, Inga Prokopenko^{79

80}, Katri Raikkonen⁵², Samuli Ripatti⁴⁰, Fernando Rivadeneira^{45

64}, Igor Rudan⁸¹, Dan Rujescu³⁴, Johannes H Smit^{14

76}, George Davey Smith⁷⁴, Jordan W Smoller^{82

83}, Nicole Soranzo⁸, Tim D Spector²⁰, Beate St Pourcain^{74

84

85}, John M Starr^{86

87}, Hreinn Stefánsson⁵⁷, Stacy Steinberg⁵⁷, Maris Teder-Laving³⁰, Gudmar Thorleifsson⁵⁷, Kári Stefánsson⁵⁷, Nicholas J Timpson⁷⁴, André G Uitterlinden^{45

64}, Cornelia M van Duijn^{45

64}, Frank J A van Rooij⁴⁵, Jaqueline M Vink^{13

88}, Peter Vollenweider⁵⁸, Eero Vuoksimaa⁴⁰, Gérard Waeber⁵⁸, Nicholas J Wareham⁹, Nicole Warrington¹, Dawn Waterworth⁸⁹, Thomas Werge^{37

65

90}, H-Erich Wichmann⁹¹, Elisabeth Widen⁴⁰, Gonneke Willemsen¹³, Alan F Wright³⁹, Margaret J Wright^{92

93}, Mousheng Xu⁹⁴, Jing Hua Zhao⁹⁵, Peter Kraft⁹⁴, David A Hinds², Cecilia M Lindgren^{60

96}, Reedik Mägi³⁰, Benjamin M Neale^{31

97}, David M Evans^{98

99}, Sarah E Medland^{100

101}

Affiliations

¹ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.
² 23andMe, Inc., Sunnyvale, CA, USA.
³ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁴ Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Karabuk University, Faculty of Business, Karabük, Turkey.
⁶ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁸ Human Genetics, Wellcome Sanger Institute, Hinxton, UK.
⁹ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
¹⁰ Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
¹¹ Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
¹² Department of Psychiatry, UMC Utrecht Brain Center, University Utrecht, Utrecht, The Netherlands.
¹³ Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
¹⁴ Amsterdam Public Health research institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
¹⁵ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
¹⁶ Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹⁷ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
¹⁸ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁹ Harvard Medical School, Boston, MA, USA.
²⁰ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
²¹ Department of Psychology, University of Edinburgh, Edinburgh, UK.
²² Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
²³ William Harvey Research Institute, Barts and the London Medical School, and the Centre for Genomic Health, Queen Mary University of London, London, UK.
²⁴ Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
²⁵ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
²⁶ Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
²⁷ Folkhälsan Research Center, Helsinki, Finland.
²⁸ Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore.
²⁹ Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³⁰ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
³¹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³² Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
³³ German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, Germany.
³⁴ University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
³⁵ Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
³⁶ Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
³⁷ Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.
³⁸ Danish Headache Center, Copenhagen University Hospital, Glostrup, Denmark.
³⁹ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁴⁰ Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
⁴¹ Institute for Biomedicine, Eurac Research, Bolzano, Italy.
⁴² Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
⁴³ Department of Genetics, Harvard Medical School, Boston, MA, USA.
⁴⁴ Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁴⁵ Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
⁴⁶ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁴⁷ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁴⁸ Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁴⁹ Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
⁵⁰ Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
⁵¹ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁵² Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁵³ Turku Institute for Advanced Studies, University of Turku, Turku, Finland.
⁵⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁵⁵ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵⁶ The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵⁷ deCODE Genetics, Reykjavik, Iceland.
⁵⁸ Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵⁹ Bristol Medical School, University of Bristol, Bristol, UK.
⁶⁰ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁶¹ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
⁶² Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
⁶³ Human Genetics, Genentech, South San Francisco, CA, USA.
⁶⁴ Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
⁶⁵ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁶⁶ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁶⁷ Service of Clinical Chemistry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶⁸ School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
⁶⁹ Department of Human Genetics, University California Los Angeles, Los Angeles, CA, USA.
⁷⁰ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
⁷¹ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷² Department of Computer Science, Columbia University, New York, NY, USA.
⁷³ Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
⁷⁴ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁷⁵ Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
⁷⁶ Department of Psychiatry, Amsterdam UMC, VU University, Amsterdam, The Netherlands.
⁷⁷ Department of Public Health, University of Split School of Medicine, Split, Croatia.
⁷⁸ Research Unit, Psychiatric Hospital Sveti Ivan, Zagreb, Croatia.
⁷⁹ Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
⁸⁰ Section of Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK.
⁸¹ Centre for Global Health Research, The Usher Institute, University of Edinburgh, Edinburgh, UK.
⁸² Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁸³ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
⁸⁴ Max Planck Institute for Psycholinguistics, Wundtlaan, Nijmegen, The Netherlands.
⁸⁵ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
⁸⁶ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁸⁷ Centre for Cognitive Ageing and Cognitive Epidemilogy, University of Edinburgh, Edinburgh, UK.
⁸⁸ Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
⁸⁹ Human Genetics, GlaxoSmithKline, Collegeville, PA, USA.
⁹⁰ The Lundbeck Foundation's IPSYCH Initiative, Copenhagen, Denmark.
⁹¹ Institute of Epidemiology, Helmholtz Center, Munich, Germany.
⁹² Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
⁹³ Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland, Australia.
⁹⁴ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
⁹⁵ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁹⁶ Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
⁹⁷ Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁹⁸ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia. d.evans1@uq.edu.au.
⁹⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. d.evans1@uq.edu.au.
¹⁰⁰ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia. Sarah.Medland@qimrberghofer.edu.au.
¹⁰¹ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Sarah.Medland@qimrberghofer.edu.au.

PMID: 32989287
PMCID: PMC7116623
DOI: 10.1038/s41562-020-00956-y

Meta-Analysis

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

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

. 2021 Jan;5(1):59-70.

doi: 10.1038/s41562-020-00956-y. Epub 2020 Sep 28.

Authors

Affiliations

¹ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.
² 23andMe, Inc., Sunnyvale, CA, USA.
³ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁴ Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Karabuk University, Faculty of Business, Karabük, Turkey.
⁶ NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁸ Human Genetics, Wellcome Sanger Institute, Hinxton, UK.
⁹ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
¹⁰ Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
¹¹ Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
¹² Department of Psychiatry, UMC Utrecht Brain Center, University Utrecht, Utrecht, The Netherlands.
¹³ Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
¹⁴ Amsterdam Public Health research institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
¹⁵ Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
¹⁶ Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
¹⁷ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
¹⁸ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁹ Harvard Medical School, Boston, MA, USA.
²⁰ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
²¹ Department of Psychology, University of Edinburgh, Edinburgh, UK.
²² Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
²³ William Harvey Research Institute, Barts and the London Medical School, and the Centre for Genomic Health, Queen Mary University of London, London, UK.
²⁴ Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
²⁵ Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
²⁶ Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
²⁷ Folkhälsan Research Center, Helsinki, Finland.
²⁸ Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore.
²⁹ Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
³⁰ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
³¹ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³² Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
³³ German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, Germany.
³⁴ University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
³⁵ Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
³⁶ Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
³⁷ Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.
³⁸ Danish Headache Center, Copenhagen University Hospital, Glostrup, Denmark.
³⁹ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
⁴⁰ Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
⁴¹ Institute for Biomedicine, Eurac Research, Bolzano, Italy.
⁴² Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
⁴³ Department of Genetics, Harvard Medical School, Boston, MA, USA.
⁴⁴ Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁴⁵ Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
⁴⁶ Department of Public Health, University of Helsinki, Helsinki, Finland.
⁴⁷ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁴⁸ Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁴⁹ Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
⁵⁰ Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
⁵¹ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁵² Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁵³ Turku Institute for Advanced Studies, University of Turku, Turku, Finland.
⁵⁴ Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
⁵⁵ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵⁶ The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁵⁷ deCODE Genetics, Reykjavik, Iceland.
⁵⁸ Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁵⁹ Bristol Medical School, University of Bristol, Bristol, UK.
⁶⁰ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁶¹ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
⁶² Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
⁶³ Human Genetics, Genentech, South San Francisco, CA, USA.
⁶⁴ Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
⁶⁵ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁶⁶ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁶⁷ Service of Clinical Chemistry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
⁶⁸ School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
⁶⁹ Department of Human Genetics, University California Los Angeles, Los Angeles, CA, USA.
⁷⁰ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
⁷¹ Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁷² Department of Computer Science, Columbia University, New York, NY, USA.
⁷³ Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
⁷⁴ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁷⁵ Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
⁷⁶ Department of Psychiatry, Amsterdam UMC, VU University, Amsterdam, The Netherlands.
⁷⁷ Department of Public Health, University of Split School of Medicine, Split, Croatia.
⁷⁸ Research Unit, Psychiatric Hospital Sveti Ivan, Zagreb, Croatia.
⁷⁹ Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
⁸⁰ Section of Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK.
⁸¹ Centre for Global Health Research, The Usher Institute, University of Edinburgh, Edinburgh, UK.
⁸² Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁸³ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
⁸⁴ Max Planck Institute for Psycholinguistics, Wundtlaan, Nijmegen, The Netherlands.
⁸⁵ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
⁸⁶ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁸⁷ Centre for Cognitive Ageing and Cognitive Epidemilogy, University of Edinburgh, Edinburgh, UK.
⁸⁸ Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
⁸⁹ Human Genetics, GlaxoSmithKline, Collegeville, PA, USA.
⁹⁰ The Lundbeck Foundation's IPSYCH Initiative, Copenhagen, Denmark.
⁹¹ Institute of Epidemiology, Helmholtz Center, Munich, Germany.
⁹² Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
⁹³ Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland, Australia.
⁹⁴ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
⁹⁵ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁹⁶ Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
⁹⁷ Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁹⁸ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia. d.evans1@uq.edu.au.
⁹⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. d.evans1@uq.edu.au.
¹⁰⁰ The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia. Sarah.Medland@qimrberghofer.edu.au.
¹⁰¹ Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Sarah.Medland@qimrberghofer.edu.au.

PMID: 32989287
PMCID: PMC7116623
DOI: 10.1038/s41562-020-00956-y

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 (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.

PubMed Disclaimer

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. 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. 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.

See this image and copyright information in PMC

Cited by

Discovery of 42 genome-wide significant loci associated with dyslexia.
Doust C, Fontanillas P, Eising E, Gordon SD, Wang Z, Alagöz G, Molz B; 23andMe Research Team; Quantitative Trait Working Group of the GenLang Consortium; Pourcain BS, Francks C, Marioni RE, Zhao J, Paracchini S, Talcott JB, Monaco AP, Stein JF, Gruen JR, Olson RK, Willcutt EG, DeFries JC, Pennington BF, Smith SD, Wright MJ, Martin NG, Auton A, Bates TC, Fisher SE, Luciano M. Doust C, et al. Nat Genet. 2022 Nov;54(11):1621-1629. doi: 10.1038/s41588-022-01192-y. Epub 2022 Oct 20. Nat Genet. 2022. PMID: 36266505 Free PMC article.
Neurology: Genetics Year in Review.
Pulst S, Pandolfo M, Roos R, Milone M, Jayadev S. Pulst S, et al. Neurol Genet. 2021 Feb 5;7(1):e556. doi: 10.1212/NXG.0000000000000556. eCollection 2021 Feb. Neurol Genet. 2021. PMID: 33889725 Free PMC article. No abstract available.
Evaluating the Association Between Genetically Proxied Neurodevelopmental Language Phenotypes and the Risk of Primary Progressive Aphasia.
Nassan M, Piras IS, Rogalski E, Geula C, Mesulam MM, Huentelman M. Nassan M, et al. Neurology. 2023 May 2;100(18):e1922-e1929. doi: 10.1212/WNL.0000000000207136. Epub 2023 Mar 8. Neurology. 2023. PMID: 36889925 Free PMC article.
Behavioral lateralization of mice varying in serotonin transporter genotype.
Stieger B, Wesseler Y, Kaiser S, Sachser N, Richter SH. Stieger B, et al. Front Behav Neurosci. 2023 Jan 11;16:1095567. doi: 10.3389/fnbeh.2022.1095567. eCollection 2022. Front Behav Neurosci. 2023. PMID: 36710954 Free PMC article.
Right- or left-handed? Protein in embryo cells might help decide.
Kulkarni S. Kulkarni S. Nature. 2024 Apr;628(8007):246. doi: 10.1038/d41586-024-00977-x. Nature. 2024. PMID: 38565906 No abstract available.

See all "Cited by" articles

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.

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources

[1] Hepper PG, McCartney GR, Shannon EA. Lateralised behaviour in first trimester human foetuses. Neuropsychologia. 1998;36:521–534. - PubMed

[2] Hepper PG, McCartney GR, Shannon EA. Lateralised behaviour in first trimester human foetuses. Neuropsychologia. 1998;36:521–534. - PubMed

[3] 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

[4] 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

[5] Lazenby R. Skeletal biology, functional asymmetry and the origins of ‘handedness’. J Theor Biol. 2002;218:129–138. - PubMed

[6] Lazenby R. Skeletal biology, functional asymmetry and the origins of ‘handedness’. J Theor Biol. 2002;218:129–138. - PubMed

[7] Gumustekin K, et al. Handedness and bilateral femoral bone densities in men and women. Int J Neurosci. 2004;114:1533–1547. - PubMed

[8] Gumustekin K, et al. Handedness and bilateral femoral bone densities in men and women. Int J Neurosci. 2004;114:1533–1547. - PubMed

[9] Steele J, Mays S. Handedness and directional asymmetry in the long bones of the human upper limb. Int J Osteoarchaeologoy. 1995;5:39–49.

[10] Steele J, Mays S. Handedness and directional asymmetry in the long bones of the human upper limb. Int J Osteoarchaeologoy. 1995;5:39–49.

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Related information

Grants and funding

LinkOut - more resources

Full Text Sources