Genome-wide association study identifies 48 common genetic variants associated with handedness,Nature Human Behaviour

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Genome-wide association study identifies 48 common genetic variants associated with handedness
Nature Human Behaviour ( IF 21.4 ) Pub Date : 2020-09-28 , DOI: 10.1038/s41562-020-00956-y
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 _{1,

74} , Sarah E Medland _{1,

98}

Affiliation

The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.
23andMe, Inc., Sunnyvale, CA, USA.
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
Karabuk University, Faculty of Business, Karabük, Turkey.
NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Human Genetics, Wellcome Sanger Institute, Hinxton, UK.
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Department of Psychiatry, UMC Utrecht Brain Center, University Utrecht, Utrecht, The Netherlands.
Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Amsterdam Public Health research institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
William Harvey Research Institute, Barts and the London Medical School, and the Centre for Genomic Health, Queen Mary University of London, London, UK.
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Folkhälsan Research Center, Helsinki, Finland.
Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore.
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Neuherberg, Germany.
University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.
Danish Headache Center, Copenhagen University Hospital, Glostrup, Denmark.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
Institute for Biomedicine, Eurac Research, Bolzano, Italy.
Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
Department of Genetics, Harvard Medical School, Boston, MA, USA.
Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Department of Public Health, University of Helsinki, Helsinki, Finland.
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
Turku Institute for Advanced Studies, University of Turku, Turku, Finland.
Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
deCODE Genetics, Reykjavik, Iceland.
Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Bristol Medical School, University of Bristol, Bristol, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
Human Genetics, Genentech, South San Francisco, CA, USA.
Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Service of Clinical Chemistry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Department of Human Genetics, University California Los Angeles, Los Angeles, CA, USA.
Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University California Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Computer Science, Columbia University, New York, NY, USA.
Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Department of Psychiatry, Amsterdam UMC, VU University, Amsterdam, The Netherlands.
Department of Public Health, University of Split School of Medicine, Split, Croatia.
Research Unit, Psychiatric Hospital Sveti Ivan, Zagreb, Croatia.
Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK.
Section of Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK.
Centre for Global Health Research, The Usher Institute, University of Edinburgh, Edinburgh, UK.
Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
Max Planck Institute for Psycholinguistics, Wundtlaan, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
Centre for Cognitive Ageing and Cognitive Epidemilogy, University of Edinburgh, Edinburgh, UK.
Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
Human Genetics, GlaxoSmithKline, Collegeville, PA, USA.
The Lundbeck Foundation's IPSYCH Initiative, Copenhagen, Denmark.
Institute of Epidemiology, Helmholtz Center, Munich, Germany.
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Centre for Advanced Imaging, The University of Queensland, Brisbane, Queensland, Australia.
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Big Data Institute at the Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

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.

中文翻译：

全基因组关联研究确定了与惯用手相关的 48 种常见遗传变异

由于惯用手与语言的关系以及左撇子在某些神经发育障碍中的比例过高，因此已被广泛研究。利用来自英国生物银行、23andMe 和国际惯用手协会的数据，我们对惯用手进行了全基因组关联荟萃分析 ( N = 1,766,671)。我们发现 41 个基因座（ P < 5 × 10 ^-8 ）与左利手相关，7 个与双手灵巧相关。组织富集分析表明中枢神经系统与惯用手的病因有关。还强调了包括微管和大脑形态调节在内的途径。我们发现左利手与神经精神特征（包括精神分裂症和双相情感障碍）之间存在暗示性的正遗传相关性。此外，左撇子和双手灵巧之间的遗传相关性较低（ r _G = 0.26），这意味着这些特征在很大程度上受到不同遗传机制的影响。我们的研究结果表明，惯用手是高度多基因的，而易患左撇子的基因变异可能是与某些精神疾病相关的部分原因。

更新日期：2020-09-28

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