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 MB Breteler; Harry Campbell; Daniel I Chasman; Lynn F Cherkas; Gail Davies; Eco JC 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; Mohammad A Ikram; Jaakko Kaprio; John P Kemp; Kay-Tee Khaw; Norman Klopp; Bettina Konte; Zoltan Kutalik; Jari Lahti; Xin Li; Ruth JF 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 WJH 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; Kari Stefansson; Nicholas J Timpson; André G Uitterlinden; Cornelia M van Duijn; Frank JA 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 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, Inês Barroso, Jacques S Beckmann, Marco P Boks, Dorret I Boomsma, Heather A Boyd, Monique MB Breteler, Harry Campbell, Daniel I Chasman, Lynn F Cherkas, Gail Davies, Eco JC de Geus, Ian J Deary, Panos Deloukas, Danielle M DickDavid 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, Mohammad A Ikram, Jaakko Kaprio, John P Kemp, Kay-Tee Khaw, Norman Klopp, Bettina Konte, Zoltan Kutalik, Jari Lahti, Xin Li, Ruth JF 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 WJH 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, Kari Stefansson, Nicholas J Timpson, André G Uitterlinden, Cornelia M van Duijn, Frank JA 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 Magi, Benjamin M Neale, David M Evans, Sarah E Medland

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

Abstract

Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively 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 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

Original language	English
Journal	Nature Human Behaviour
Early online date	28 Sept 2020
DOIs	https://doi.org/10.1038/s41562-020-00956-y
Publication status	E-pub ahead of print - 28 Sept 2020

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10.1038/s41562-020-00956-y

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Partida, G. C., 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. MB., Campbell, H., Chasman, D. I., Cherkas, L. F., Davies, G., de Geus, E. JC., Deary, I. J., Deloukas, P., ... Medland, S. E. (2020). Genome-wide association study identifies 48 common genetic variants associated with handedness. Nature Human Behaviour. Advance online publication. https://doi.org/10.1038/s41562-020-00956-y

@article{3347497ff778463b9125c8dbfbe6f55b,

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

abstract = "Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively 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 32 studies from the International Handedness Consortium, we conducted the world{\textquoteright}s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.",

author = "Partida, {Gabriel Cuellar} 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 MB} and Harry Campbell and Chasman, {Daniel I} and Cherkas, {Lynn F} and Gail Davies and {de Geus}, {Eco JC} 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 Jouke-Jan Hottenga and Huffman, {Jennifer E} and Liang-Dar Hwang and Ikram, {Mohammad A} 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 JF} 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 WJH} 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 {St Pourcain}, Beate and Starr, {John M} and Hreinn Stef{\'a}nsson and Stacy Steinberg and Maris Teder-Laving and Gudmar Thorleifsson and Kari Stefansson and Timpson, {Nicholas J} and Uitterlinden, {Andr{\'e} G} and {van Duijn}, {Cornelia M} and {van Rooij}, {Frank JA} 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 H.-Erich Wichmann 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 = "2020",

month = sep,

day = "28",

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

language = "English",

journal = "Nature Human Behaviour",

issn = "2397-3374",

publisher = "Nature Publishing Group",

}

Partida, GC, 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, 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, St Pourcain, B, Starr, JM, Stefánsson, 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 2020, 'Genome-wide association study identifies 48 common genetic variants associated with handedness', Nature Human Behaviour. 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 - Partida, Gabriel Cuellar

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 MB

AU - Campbell, Harry

AU - Chasman, Daniel I

AU - Cherkas, Lynn F

AU - Davies, Gail

AU - de Geus, Eco JC

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, Mohammad A

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 JF

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 WJH

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 - St Pourcain, Beate

AU - Starr, John M

AU - Stefánsson, Hreinn

AU - Steinberg, Stacy

AU - Teder-Laving, Maris

AU - Thorleifsson, Gudmar

AU - Stefansson, Kari

AU - Timpson, Nicholas J

AU - Uitterlinden, André G

AU - van Duijn, Cornelia M

AU - van Rooij, Frank JA

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 - Magi, Reedik

AU - Neale, Benjamin M

AU - Evans, David M

AU - Medland, Sarah E

PY - 2020/9/28

Y1 - 2020/9/28

N2 - Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively 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 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

AB - Handedness, a consistent asymmetry in skill or use of the hands, has been studied extensively 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 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

U2 - 10.1038/s41562-020-00956-y

DO - 10.1038/s41562-020-00956-y

M3 - Article

SN - 2397-3374

JO - Nature Human Behaviour

JF - Nature Human Behaviour

ER -

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

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