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

G Cuellar-Partida; JY Tung; N Eriksson; E Albrecht; F Aliev; OA Andreassen; I Barroso; JS Beckmann; M P Boks; DI Boomsma; HA Boyd; Monique Breteler; H Campbell; DI Chasman; LF Cherkas; G Davies; EJCN de Geus; IJ Deary; P Deloukas; DM Dick; DL Duffy; JG Eriksson; T Esko; B Feenstra; F Geller; C Gieger; I Giegling; SD Gordon; J Han; TF Hansen; AM Hartmann; C Hayward; K Heikkilä; AA Hicks; JN Hirschhorn; JJ Hottenga; JE Huffman; LD Hwang; Arfan Ikram; J Kaprio; JP Kemp; KTH Khaw; N Klopp; B Konte; Z Kutalik; J Lahti; X Li; RJ Loos; M Luciano; SH Magnusson; M Mangino; P Marques-Vidal; NG Martin; WL McArdle; MI McCarthy; Maria Medina Gomez; M Melbye; SA Melville; A Metspalu; L Milani; V Mooser; M Nelis; DR Nyholt; KS O’Connell; Roel Ophoff; C Palmer; A Palotie; T Palviainen; G Pare; L Paternoster; L Peltonen; BWJH Penninx; O Polasek; PP Pramstaller; I Prokopenko; K Raikkonen; S Ripatti; Fernando Rivadeneira; I Rudan; D Rujescu; JH Smit; GD Smith; JW Smoller; N Soranzo; TD Spector; BS Pourcain; JM Starr; H Stefánsson; S Steinberg; M Teder-Laving; G Thorleifsson; K Stefánsson; NJ Timpson; André Uitterlinden; Cornelia Duijn; FJA van Rooij; JM Vink; P Vollenweider; E Vuoksimaa; G Waeber; NJ Wareham; N Warrington; D Waterworth; T Werge; HE Wichmann; E Widen; G Willemsen; AF Wright; MJ Wright; M Xu; JH Zhao; P Kraft; DA Hinds; CM Lindgren; R Mägi; BM Neale; DM Evans; SE Medland

doi:10.1038/s41562-020-00956-y

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

G Cuellar-Partida, JY Tung, N Eriksson, E Albrecht, F Aliev, OA Andreassen, I Barroso, JS Beckmann, M P Boks, DI Boomsma, HA Boyd, Monique Breteler, H Campbell, DI Chasman, LF Cherkas, G Davies, EJCN de Geus, IJ Deary, P Deloukas, DM DickDL Duffy, JG Eriksson, T Esko, B Feenstra, F Geller, C Gieger, I Giegling, SD Gordon, J Han, TF Hansen, AM Hartmann, C Hayward, K Heikkilä, AA Hicks, JN Hirschhorn, JJ Hottenga, JE Huffman, LD Hwang, Arfan Ikram, J Kaprio, JP Kemp, KTH Khaw, N Klopp, B Konte, Z Kutalik, J Lahti, X Li, RJ Loos, M Luciano, SH Magnusson, M Mangino, P Marques-Vidal, NG Martin, WL McArdle, MI McCarthy, Maria Medina Gomez, M Melbye, SA Melville, A Metspalu, L Milani, V Mooser, M Nelis, DR Nyholt, KS O’Connell, Roel Ophoff, C Palmer, A Palotie, T Palviainen, G Pare, L Paternoster, L Peltonen, BWJH Penninx, O Polasek, PP Pramstaller, I Prokopenko, K Raikkonen, S Ripatti, Fernando Rivadeneira, I Rudan, D Rujescu, JH Smit, GD Smith, JW Smoller, N Soranzo, TD Spector, BS Pourcain, JM Starr, H Stefánsson, S Steinberg, M Teder-Laving, G Thorleifsson, K Stefánsson, NJ Timpson, André Uitterlinden, Cornelia Duijn, FJA van Rooij, JM Vink, P Vollenweider, E Vuoksimaa, G Waeber, NJ Wareham, N Warrington, D Waterworth, T Werge, HE Wichmann, E Widen, G Willemsen, AF Wright, MJ Wright, M Xu, JH Zhao, P Kraft, DA Hinds, CM Lindgren, R Mägi, BM Neale, DM Evans, SE Medland

Research output: Contribution to journal › Article › Academic › 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 × 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

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10.1038/s41562-020-00956-y

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116623/

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Cuellar-Partida, G., Tung, JY., Eriksson, N., Albrecht, E., Aliev, F., Andreassen, OA., Barroso, I., Beckmann, JS., Boks, M. P., Boomsma, DI., Boyd, HA., Breteler, M., Campbell, H., Chasman, DI., Cherkas, LF., Davies, G., de Geus, EJCN., Deary, IJ., Deloukas, P., ... Medland, SE. (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{f6d7ad83b9d14cc1b81b5d34ba8f141d,

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 = "G Cuellar-Partida and JY Tung and N Eriksson and E Albrecht and F Aliev and OA Andreassen and I Barroso and JS Beckmann and Boks, {M P} and DI Boomsma and HA Boyd and Monique Breteler and H Campbell and DI Chasman and LF Cherkas and G Davies and {de Geus}, EJCN and IJ Deary and P Deloukas and DM Dick and DL Duffy and JG Eriksson and T Esko and B Feenstra and F Geller and C Gieger and I Giegling and SD Gordon and J Han and TF Hansen and AM Hartmann and C Hayward and K Heikkil{\"a} and AA Hicks and JN Hirschhorn and JJ Hottenga and JE Huffman and LD Hwang and Arfan Ikram and J Kaprio and JP Kemp and KTH Khaw and N Klopp and B Konte and Z Kutalik and J Lahti and X Li and RJ Loos and M Luciano and SH Magnusson and M Mangino and P Marques-Vidal and NG Martin and WL McArdle and MI McCarthy and {Medina Gomez}, Maria and M Melbye and SA Melville and A Metspalu and L Milani and V Mooser and M Nelis and DR Nyholt and KS O{\textquoteright}Connell and Roel Ophoff and C Palmer and A Palotie and T Palviainen and G Pare and L Paternoster and L Peltonen and BWJH Penninx and O Polasek and PP Pramstaller and I Prokopenko and K Raikkonen and S Ripatti and Fernando Rivadeneira and I Rudan and D Rujescu and JH Smit and GD Smith and JW Smoller and N Soranzo and TD Spector and BS Pourcain and JM Starr and H Stef{\'a}nsson and S Steinberg and M Teder-Laving and G Thorleifsson and K Stef{\'a}nsson and NJ Timpson and Andr{\'e} Uitterlinden and Cornelia Duijn and {van Rooij}, FJA and JM Vink and P Vollenweider and E Vuoksimaa and G Waeber and NJ Wareham and N Warrington and D Waterworth and T Werge and HE Wichmann and E Widen and G Willemsen and AF Wright and MJ Wright and M Xu and JH Zhao and P Kraft and DA Hinds and CM Lindgren and R M{\"a}gi and BM Neale and DM Evans and SE Medland",

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, M, Campbell, H, Chasman, DI, Cherkas, LF, Davies, G, de Geus, EJCN, 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, A, Kaprio, J, Kemp, JP, Khaw, KTH, Klopp, N, Konte, B, Kutalik, Z, Lahti, J, Li, X, Loos, RJ, Luciano, M, Magnusson, SH, Mangino, M, Marques-Vidal, P, Martin, NG, McArdle, WL, McCarthy, MI, Medina Gomez, M, Melbye, M, Melville, SA, Metspalu, A, Milani, L, Mooser, V, Nelis, M, Nyholt, DR, O’Connell, KS, Ophoff, R, 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, A, Duijn, C, 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, G

AU - Tung, JY

AU - Eriksson, N

AU - Albrecht, E

AU - Aliev, F

AU - Andreassen, OA

AU - Barroso, I

AU - Beckmann, JS

AU - Boks, M P

AU - Boomsma, DI

AU - Boyd, HA

AU - Breteler, Monique

AU - Campbell, H

AU - Chasman, DI

AU - Cherkas, LF

AU - Davies, G

AU - de Geus, EJCN

AU - Deary, IJ

AU - Deloukas, P

AU - Dick, DM

AU - Duffy, DL

AU - Eriksson, JG

AU - Esko, T

AU - Feenstra, B

AU - Geller, F

AU - Gieger, C

AU - Giegling, I

AU - Gordon, SD

AU - Han, J

AU - Hansen, TF

AU - Hartmann, AM

AU - Hayward, C

AU - Heikkilä, K

AU - Hicks, AA

AU - Hirschhorn, JN

AU - Hottenga, JJ

AU - Huffman, JE

AU - Hwang, LD

AU - Ikram, Arfan

AU - Kaprio, J

AU - Kemp, JP

AU - Khaw, KTH

AU - Klopp, N

AU - Konte, B

AU - Kutalik, Z

AU - Lahti, J

AU - Li, X

AU - Loos, RJ

AU - Luciano, M

AU - Magnusson, SH

AU - Mangino, M

AU - Marques-Vidal, P

AU - Martin, NG

AU - McArdle, WL

AU - McCarthy, MI

AU - Medina Gomez, Maria

AU - Melbye, M

AU - Melville, SA

AU - Metspalu, A

AU - Milani, L

AU - Mooser, V

AU - Nelis, M

AU - Nyholt, DR

AU - O’Connell, KS

AU - Ophoff, Roel

AU - Palmer, C

AU - Palotie, A

AU - Palviainen, T

AU - Pare, G

AU - Paternoster, L

AU - Peltonen, L

AU - Penninx, BWJH

AU - Polasek, O

AU - Pramstaller, PP

AU - Prokopenko, I

AU - Raikkonen, K

AU - Ripatti, S

AU - Rivadeneira, Fernando

AU - Rudan, I

AU - Rujescu, D

AU - Smit, JH

AU - Smith, GD

AU - Smoller, JW

AU - Soranzo, N

AU - Spector, TD

AU - Pourcain, BS

AU - Starr, JM

AU - Stefánsson, H

AU - Steinberg, S

AU - Teder-Laving, M

AU - Thorleifsson, G

AU - Stefánsson, K

AU - Timpson, NJ

AU - Uitterlinden, André

AU - Duijn, Cornelia

AU - van Rooij, FJA

AU - Vink, JM

AU - Vollenweider, P

AU - Vuoksimaa, E

AU - Waeber, G

AU - Wareham, NJ

AU - Warrington, N

AU - Waterworth, D

AU - Werge, T

AU - Wichmann, HE

AU - Widen, E

AU - Willemsen, G

AU - Wright, AF

AU - Wright, MJ

AU - Xu, M

AU - Zhao, JH

AU - Kraft, P

AU - Hinds, DA

AU - Lindgren, CM

AU - Mägi, R

AU - Neale, BM

AU - Evans, DM

AU - Medland, SE

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 - http://www.scopus.com/inward/record.url?scp=85091609696&partnerID=8YFLogxK

U2 - 10.1038/s41562-020-00956-y

DO - 10.1038/s41562-020-00956-y

M3 - Article

C2 - 32989287

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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