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. Dick; David 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

doi:10.1038/s41562-020-00956-y

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. Dick

David 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

University of Queensland
23andMe Inc.
Helmholtz Zentrum München - German Research Center for Environmental Health
Virginia Commonwealth University
Karabuk University
University of Oslo
Wellcome Trust Sanger Institute
University of Cambridge
University of Lausanne
Utrecht University
Vrije Universiteit Amsterdam
Amsterdam UMC
Statens Serum Institut
German Center for Neurodegenerative Diseases
University of Edinburgh
Brigham and Women’s Hospital
Harvard University
King's College London
Queen Mary University of London
Queensland Institute of Medical Research
Helsinki University Hospital
Folkhalsan
Agency for Science, Technology and Research, Singapore
National University of Singapore
University of Tartu
Broad Institute
German Center for Diabetes Research
Martin Luther University Halle-Wittenberg
Indiana University-Purdue University Indianapolis
Institute of Biological Psychiatry
University of Copenhagen
University of Helsinki
EURAC Research
Boston Children's Hospital
Erasmus University Rotterdam
University of Bristol
Hannover Medical School
Swiss Institute of Bioinformatics
University of Turku
Icahn School of Medicine at Mount Sinai
deCODE Genetics
University of Oxford
Oxford University Hospitals NHS Foundation Trust
Genentech Incorporated
Stanford University
Queensland University of Technology
University of California at Los Angeles
Columbia University
McMaster University
University of Split
Psychiatric Hospital Sveti Ivan
University of Surrey
Imperial College London
Massachusetts General Hospital
Max Planck Institute for Psycholinguistics
Radboud University Nijmegen
GlaxoSmithKline
H. Lundbeck A/S

Research output: Contribution to journal › Article › peer-review

108 Citations (Scopus)

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.

Original language	English
Pages (from-to)	59-70
Number of pages	12
Journal	Nature Human Behaviour
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s41562-020-00956-y
Publication status	Published - Jan 2021
Externally published	Yes

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10.1038/s41562-020-00956-y

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Cuellar-Partida, G., Tung, J. Y., Eriksson, N., Albrecht, E., Aliev, F., Andreassen, O. A., Barroso, I., Beckmann, J. S., Boks, M. P., Boomsma, D. I., Boyd, H. A., Breteler, M. M. B., Campbell, H., Chasman, D. I., Cherkas, L. F., Davies, G., de Geus, E. J. C., Deary, I. J., Deloukas, P., ... Medland, S. E. (2021). Genome-wide association study identifies 48 common genetic variants associated with handedness. Nature Human Behaviour, 5(1), 59-70. https://doi.org/10.1038/s41562-020-00956-y

@article{184674aa0f654617a6a1a322a86b4f8d,

title = "Genome-wide association study identifies 48 common genetic variants associated with handedness",

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.",

author = "Gabriel Cuellar-Partida and Tung, \{Joyce Y.\} and Nicholas Eriksson and Eva Albrecht and Fazil Aliev and Andreassen, \{Ole A.\} and In{\^e}s Barroso and Beckmann, \{Jacques S.\} and Boks, \{Marco P.\} and Boomsma, \{Dorret I.\} and Boyd, \{Heather A.\} and Breteler, \{Monique M.B.\} and Harry Campbell and Chasman, \{Daniel I.\} and Cherkas, \{Lynn F.\} and Gail Davies and \{de Geus\}, \{Eco J.C.\} and Deary, \{Ian J.\} and Panos Deloukas and Dick, \{Danielle M.\} and Duffy, \{David L.\} and Eriksson, \{Johan G.\} and T{\~o}nu Esko and Bjarke Feenstra and Frank Geller and Christian Gieger and Ina Giegling and Gordon, \{Scott D.\} and Jiali Han and Hansen, \{Thomas F.\} and Hartmann, \{Annette M.\} and Caroline Hayward and Kauko Heikkil{\"a} and Hicks, \{Andrew A.\} and Hirschhorn, \{Joel N.\} and Hottenga, \{Jouke Jan\} and Huffman, \{Jennifer E.\} and Hwang, \{Liang Dar\} and Ikram, \{M. Arfan\} and Jaakko Kaprio and Kemp, \{John P.\} and Khaw, \{Kay Tee\} and Norman Klopp and Bettina Konte and Zoltan Kutalik and Jari Lahti and Xin Li and Loos, \{Ruth J.F.\} and Michelle Luciano and Magnusson, \{Sigurdur H.\} and Massimo Mangino and Pedro Marques-Vidal and Martin, \{Nicholas G.\} and McArdle, \{Wendy L.\} and McCarthy, \{Mark I.\} and Carolina Medina-Gomez and Mads Melbye and Melville, \{Scott A.\} and Andres Metspalu and Lili Milani and Vincent Mooser and Mari Nelis and Nyholt, \{Dale R.\} and O{\textquoteright}Connell, \{Kevin S.\} and Ophoff, \{Roel A.\} and Cameron Palmer and Aarno Palotie and Teemu Palviainen and Guillaume Pare and Lavinia Paternoster and Leena Peltonen and Penninx, \{Brenda W.J.H.\} and Ozren Polasek and Pramstaller, \{Peter P.\} and Inga Prokopenko and Katri Raikkonen and Samuli Ripatti and Fernando Rivadeneira and Igor Rudan and Dan Rujescu and Smit, \{Johannes H.\} and Smith, \{George Davey\} and Smoller, \{Jordan W.\} and Nicole Soranzo and Spector, \{Tim D.\} and Pourcain, \{Beate St\} and Starr, \{John M.\} and Hreinn Stef{\'a}nsson and Stacy Steinberg and Maris Teder-Laving and Gudmar Thorleifsson and K{\'a}ri Stef{\'a}nsson and Timpson, \{Nicholas J.\} and Uitterlinden, \{Andr{\'e} G.\} and \{van Duijn\}, \{Cornelia M.\} and \{van Rooij\}, \{Frank J.A.\} and Vink, \{Jaqueline M.\} and Peter Vollenweider and Eero Vuoksimaa and G{\'e}rard Waeber and Wareham, \{Nicholas J.\} and Nicole Warrington and Dawn Waterworth and Thomas Werge and Wichmann, \{H. Erich\} and Elisabeth Widen and Gonneke Willemsen and Wright, \{Alan F.\} and Wright, \{Margaret J.\} and Mousheng Xu and Zhao, \{Jing Hua\} and Peter Kraft and Hinds, \{David A.\} and Lindgren, \{Cecilia M.\} and Reedik M{\"a}gi and Neale, \{Benjamin M.\} and Evans, \{David M.\} and Medland, \{Sarah E.\}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = jan,

doi = "10.1038/s41562-020-00956-y",

language = "English",

volume = "5",

pages = "59--70",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

number = "1",

}

Cuellar-Partida, G, Tung, JY, Eriksson, N, Albrecht, E, Aliev, F, Andreassen, OA, Barroso, I, Beckmann, JS, Boks, MP, Boomsma, DI, Boyd, HA, Breteler, MMB, Campbell, H, Chasman, DI, Cherkas, LF, Davies, G, de Geus, EJC, Deary, IJ, Deloukas, P, Dick, DM, Duffy, DL, Eriksson, JG, Esko, T, Feenstra, B, Geller, F, Gieger, C, Giegling, I, Gordon, SD, Han, J, Hansen, TF, Hartmann, AM, Hayward, C, Heikkilä, K, Hicks, AA, Hirschhorn, JN, Hottenga, JJ, Huffman, JE, Hwang, LD, Ikram, MA, Kaprio, J, Kemp, JP, Khaw, KT, Klopp, N, Konte, B, Kutalik, Z, Lahti, J, Li, X, Loos, RJF, Luciano, M, Magnusson, SH, Mangino, M, Marques-Vidal, P, Martin, NG, McArdle, WL, McCarthy, MI, Medina-Gomez, C, Melbye, M, Melville, SA, Metspalu, A, Milani, L, Mooser, V, Nelis, M, Nyholt, DR, O’Connell, KS, Ophoff, RA, Palmer, C, Palotie, A, Palviainen, T, Pare, G, Paternoster, L, Peltonen, L, Penninx, BWJH, Polasek, O, Pramstaller, PP, Prokopenko, I, Raikkonen, K, Ripatti, S, Rivadeneira, F, Rudan, I, Rujescu, D, Smit, JH, Smith, GD, Smoller, JW, Soranzo, N, Spector, TD, Pourcain, BS, Starr, JM, Stefánsson, H, Steinberg, S, Teder-Laving, M, Thorleifsson, G, Stefánsson, K, Timpson, NJ, Uitterlinden, AG, van Duijn, CM, van Rooij, FJA, Vink, JM, Vollenweider, P, Vuoksimaa, E, Waeber, G, Wareham, NJ, Warrington, N, Waterworth, D, Werge, T, Wichmann, HE, Widen, E, Willemsen, G, Wright, AF, Wright, MJ, Xu, M, Zhao, JH, Kraft, P, Hinds, DA, Lindgren, CM, Mägi, R, Neale, BM, Evans, DM & Medland, SE 2021, 'Genome-wide association study identifies 48 common genetic variants associated with handedness', Nature Human Behaviour, vol. 5, no. 1, pp. 59-70. https://doi.org/10.1038/s41562-020-00956-y

TY - JOUR

T1 - Genome-wide association study identifies 48 common genetic variants associated with handedness

AU - Cuellar-Partida, Gabriel

AU - Tung, Joyce Y.

AU - Eriksson, Nicholas

AU - Albrecht, Eva

AU - Aliev, Fazil

AU - Andreassen, Ole A.

AU - Barroso, Inês

AU - Beckmann, Jacques S.

AU - Boks, Marco P.

AU - Boomsma, Dorret I.

AU - Boyd, Heather A.

AU - Breteler, Monique M.B.

AU - Campbell, Harry

AU - Chasman, Daniel I.

AU - Cherkas, Lynn F.

AU - Davies, Gail

AU - de Geus, Eco J.C.

AU - Deary, Ian J.

AU - Deloukas, Panos

AU - Dick, Danielle M.

AU - Duffy, David L.

AU - Eriksson, Johan G.

AU - Esko, Tõnu

AU - Feenstra, Bjarke

AU - Geller, Frank

AU - Gieger, Christian

AU - Giegling, Ina

AU - Gordon, Scott D.

AU - Han, Jiali

AU - Hansen, Thomas F.

AU - Hartmann, Annette M.

AU - Hayward, Caroline

AU - Heikkilä, Kauko

AU - Hicks, Andrew A.

AU - Hirschhorn, Joel N.

AU - Hottenga, Jouke Jan

AU - Huffman, Jennifer E.

AU - Hwang, Liang Dar

AU - Ikram, M. Arfan

AU - Kaprio, Jaakko

AU - Kemp, John P.

AU - Khaw, Kay Tee

AU - Klopp, Norman

AU - Konte, Bettina

AU - Kutalik, Zoltan

AU - Lahti, Jari

AU - Li, Xin

AU - Loos, Ruth J.F.

AU - Luciano, Michelle

AU - Magnusson, Sigurdur H.

AU - Mangino, Massimo

AU - Marques-Vidal, Pedro

AU - Martin, Nicholas G.

AU - McArdle, Wendy L.

AU - McCarthy, Mark I.

AU - Medina-Gomez, Carolina

AU - Melbye, Mads

AU - Melville, Scott A.

AU - Metspalu, Andres

AU - Milani, Lili

AU - Mooser, Vincent

AU - Nelis, Mari

AU - Nyholt, Dale R.

AU - O’Connell, Kevin S.

AU - Ophoff, Roel A.

AU - Palmer, Cameron

AU - Palotie, Aarno

AU - Palviainen, Teemu

AU - Pare, Guillaume

AU - Paternoster, Lavinia

AU - Peltonen, Leena

AU - Penninx, Brenda W.J.H.

AU - Polasek, Ozren

AU - Pramstaller, Peter P.

AU - Prokopenko, Inga

AU - Raikkonen, Katri

AU - Ripatti, Samuli

AU - Rivadeneira, Fernando

AU - Rudan, Igor

AU - Rujescu, Dan

AU - Smit, Johannes H.

AU - Smith, George Davey

AU - Smoller, Jordan W.

AU - Soranzo, Nicole

AU - Spector, Tim D.

AU - Pourcain, Beate St

AU - Starr, John M.

AU - Stefánsson, Hreinn

AU - Steinberg, Stacy

AU - Teder-Laving, Maris

AU - Thorleifsson, Gudmar

AU - Stefánsson, Kári

AU - Timpson, Nicholas J.

AU - Uitterlinden, André G.

AU - van Duijn, Cornelia M.

AU - van Rooij, Frank J.A.

AU - Vink, Jaqueline M.

AU - Vollenweider, Peter

AU - Vuoksimaa, Eero

AU - Waeber, Gérard

AU - Wareham, Nicholas J.

AU - Warrington, Nicole

AU - Waterworth, Dawn

AU - Werge, Thomas

AU - Wichmann, H. Erich

AU - Widen, Elisabeth

AU - Willemsen, Gonneke

AU - Wright, Alan F.

AU - Wright, Margaret J.

AU - Xu, Mousheng

AU - Zhao, Jing Hua

AU - Kraft, Peter

AU - Hinds, David A.

AU - Lindgren, Cecilia M.

AU - Mägi, Reedik

AU - Neale, Benjamin M.

AU - Evans, David M.

AU - Medland, Sarah E.

PY - 2021/1

Y1 - 2021/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85091609696

U2 - 10.1038/s41562-020-00956-y

DO - 10.1038/s41562-020-00956-y

M3 - Article

C2 - 32989287

AN - SCOPUS:85091609696

SN - 2397-3374

VL - 5

SP - 59

EP - 70

JO - Nature Human Behaviour

JF - Nature Human Behaviour

IS - 1

ER -

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

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