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; Ines 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; Tonu Esko; Bjarke Feenstra; Frank Geller; Christian Gieger; Ina Giegling; Scott D. Gordon; Jiali Han; Thomas F. Hansen; Annette M. Hartmann; Caroline Hayward; Kauko Heikkila; 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 Stefansson; Stacy Steinberg; Maris Teder-Laving; Gudmar Thorleifsson; Kari Stefansson; Nicholas J. Timpson; Andre G. Uitterlinden; Cornelia M. van Duijn; Frank J. A. van Rooij; Jaqueline M. Vink; Peter Vollenweider; Eero Vuoksimaa; Gerard 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 Magi; 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, Ines 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, Tonu Esko, Bjarke Feenstra, Frank Geller, Christian Gieger, Ina Giegling, Scott D. Gordon, Jiali Han, Thomas F. Hansen, Annette M. Hartmann, Caroline Hayward, Kauko Heikkila, 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 Stefansson, Stacy Steinberg, Maris Teder-Laving, Gudmar Thorleifsson, Kari Stefansson, Nicholas J. Timpson, Andre G. Uitterlinden, Cornelia M. van Duijn, Frank J. A. van Rooij, Jaqueline M. Vink, Peter Vollenweider, Eero Vuoksimaa, Gerard 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 Magi, Benjamin M. Neale, David M. Evans, Sarah E. Medland

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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 x 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.

A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.

Originalsprog	Engelsk
Tidsskrift	Nature Human Behaviour
Vol/bind	5
Sider (fra-til)	59-70
ISSN	2397-3374
DOI	https://doi.org/10.1038/s41562-020-00956-y
Status	Udgivet - 2021

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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, 59-70. https://doi.org/10.1038/s41562-020-00956-y

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, Heikkila, K, Hicks, AA, Hirschhorn, JN, Hottenga, J-J, Huffman, JE, Hwang, L-D, Ikram, MA, Kaprio, J, Kemp, JP, Khaw, K-T, 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, Stefansson, H, Steinberg, S, Teder-Laving, M, Thorleifsson, G, Stefansson, 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, H-E, Widen, E, Willemsen, G, Wright, AF, Wright, MJ, Xu, M, Zhao, JH, Kraft, P, Hinds, DA, Lindgren, CM, Magi, R, Neale, BM, Evans, DM & Medland, SE 2021, 'Genome-wide association study identifies 48 common genetic variants associated with handedness', Nature Human Behaviour, bind 5, s. 59-70. https://doi.org/10.1038/s41562-020-00956-y

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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 x 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.A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.",

keywords = "LANGUAGE DOMINANCE, LINKAGE ANALYSIS, METAANALYSIS, MICROTUBULE, ASYMMETRY, AUTISM, LATERALIZATION, SCHIZOPHRENIA, ORIGINS, SCREEN",

author = "Gabriel Cuellar-Partida and Tung, {Joyce Y.} and Nicholas Eriksson and Eva Albrecht and Fazil Aliev and Andreassen, {Ole A.} and Ines 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 Tonu 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 Heikkila and Hicks, {Andrew A.} and Hirschhorn, {Joel N.} and Jouke-Jan Hottenga and Huffman, {Jennifer E.} and Liang-Dar Hwang and Ikram, {M. Arfan} and Jaakko Kaprio and Kemp, {John P.} and Kay-Tee Khaw 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'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 Stefansson and Stacy Steinberg and Maris Teder-Laving and Gudmar Thorleifsson and Kari Stefansson and Timpson, {Nicholas J.} and Uitterlinden, {Andre G.} and {van Duijn}, {Cornelia M.} and {van Rooij}, {Frank J. A.} and Vink, {Jaqueline M.} and Peter Vollenweider and Eero Vuoksimaa and Gerard 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 Magi and Neale, {Benjamin M.} and Evans, {David M.} and Medland, {Sarah E.}",

year = "2021",

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",

}

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, Ines

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, Tonu

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 - Heikkila, 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 - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Teder-Laving, Maris

AU - Thorleifsson, Gudmar

AU - Stefansson, Kari

AU - Timpson, Nicholas J.

AU - Uitterlinden, Andre G.

AU - van Duijn, Cornelia M.

AU - van Rooij, Frank J. A.

AU - Vink, Jaqueline M.

AU - Vollenweider, Peter

AU - Vuoksimaa, Eero

AU - Waeber, Gerard

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 - Magi, Reedik

AU - Neale, Benjamin M.

AU - Evans, David M.

AU - Medland, Sarah E.

PY - 2021

Y1 - 2021

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 x 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.A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.

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 x 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.A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.

KW - LANGUAGE DOMINANCE

KW - LINKAGE ANALYSIS

KW - METAANALYSIS

KW - MICROTUBULE

KW - ASYMMETRY

KW - AUTISM

KW - LATERALIZATION

KW - SCHIZOPHRENIA

KW - ORIGINS

KW - SCREEN

U2 - 10.1038/s41562-020-00956-y

DO - 10.1038/s41562-020-00956-y

M3 - Journal article

C2 - 32989287

SN - 2397-3374

VL - 5

SP - 59

EP - 70

JO - Nature Human Behaviour

JF - Nature Human Behaviour

ER -