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

被引：93

作者：

Cuellar-Partida, Gabriel ^{[1
,2
]}

Tung, Joyce Y. ^{[2
]}

Eriksson, Nicholas ^{[2
]}

Albrecht, Eva ^{[3
]}

Aliev, Fazil ^{[4
,5
]}

Andreassen, Ole A. ^{[6
,7
]}

Barroso, Ines ^{[8
,9
,10
]}

Beckmann, Jacques S. ^{[11
,12
]}

Boks, Marco P. ^{[13
]}

Boomsma, Dorret I. ^{[14
,15
]}

Boyd, Heather A. ^{[16
]}

Breteler, Monique M. B. ^{[17
]}

Campbell, Harry ^{[18
]}

Chasman, Daniel I. ^{[19
,20
]}

Cherkas, Lynn F. ^{[21
]}

Davies, Gail ^{[22
,23
]}

de Geus, Eco J. C. ^{[14
,15
]}

Deary, Ian J. ^{[22
,23
]}

Deloukas, Panos ^{[24
,25
]}

Dick, Danielle M. ^{[4
,26
]}

Duffy, David L. ^{[27
]}

Eriksson, Johan G. ^{[28
,29
,30
,31
,32
]}

Esko, Tonu ^{[33
,34
]}

Feenstra, Bjarke ^{[16
]}

Geller, Frank ^{[16
]}

Gieger, Christian ^{[35
,36
]}

Giegling, Ina ^{[37
,38
]}

Gordon, Scott D. ^{[27
]}

Han, Jiali ^{[39
,40
]}

Hansen, Thomas F. ^{[41
,42
]}

Hartmann, Annette M. ^{[37
,38
]}

Hayward, Caroline ^{[43
]}

Heikkila, Kauko ^{[44
]}

Hicks, Andrew A. ^{[45
]}

Hirschhorn, Joel N. ^{[46
,47
,48
]}

Hottenga, Jouke-Jan ^{[14
,15
]}

Huffman, Jennifer E. ^{[43
]}

Hwang, Liang-Dar ^{[1
]}

Ikram, M. Arfan ^{[49
]}

Kaprio, Jaakko ^{[44
,50
]}

Kemp, John P. ^{[1
,51
]}

Khaw, Kay-Tee ^{[52
]}

Klopp, Norman ^{[53
]}

Konte, Bettina ^{[37
,38
]}

Kutalik, Zoltan ^{[54
,55
]}

Lahti, Jari ^{[56
,57
,58
]}

Li, Xin ^{[39
,40
]}

Loos, Ruth J. F. ^{[9
,59
,60
]}

Luciano, Michelle ^{[22
,23
]}

Magnusson, Sigurdur H. ^{[61
]}

机构：

[1] Univ Queensland, Diamantina Inst, Woolloongabba, Qld, Australia

[2] 23andMe Inc, Sunnyvale, CA USA

[3] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany

[4] Virginia Commonwealth Univ, Dept Psychol, Box 2018, Richmond, VA 23284 USA

[5] Karabuk Univ, Fac Business, Karabuk, Turkey

[6] Univ Oslo, Inst Clin Med, NORMENT, Oslo, Norway

[7] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway

[8] Wellcome Sanger Inst, Human Genet, Hinxton, England

[9] Univ Cambridge, MRC Epidemiol Unit, Cambridge, England

[10] Univ Cambridge, Wellcome MRC Inst Metab Sci, Cambridge, England

[11] CHU Vaudois, Serv Med Genet, Lausanne, Switzerland

[12] Univ Lausanne, Lausanne, Switzerland

[13] Univ Utrecht, UMC Utrecht Brain Ctr, Dept Psychiat, Utrecht, Netherlands

[14] Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands

[15] Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Med Ctr, Amsterdam, Netherlands

[16] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

[17] German Ctr Neurodegenerat Dis DZNE, Populat Hlth Sci, Bonn, Germany

[18] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

[19] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[20] Harvard Med Sch, Boston, MA 02115 USA

[21] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

[22] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[23] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[24] Queen Mary Univ London, William Harvey Res Inst, Barts & London Med Sch, London, England

[25] Queen Mary Univ London, Ctr Genom Hlth, London, England

[26] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA

[27] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia

[28] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland

[29] Helsinki Univ Hosp, Helsinki, Finland

[30] Folkhalsan Res Ctr, Helsinki, Finland

[31] Agcy Sci Technol & Res, Singapore Inst Clin Sci, Singapore, Singapore

[32] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynaecol, Singapore, Singapore

[33] Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia

[34] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[35] German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[36] German Ctr Diabet Res DZD, Neuherberg, Germany

[37] Martin Luther Univ Halle Wittenberg, Univ Clin, Halle, Saale, Germany

[38] Martin Luther Univ Halle Wittenberg, Outpatient Clin Psychiat Psychotherapy & Psychoso, Halle, Saale, Germany

[39] Indiana Univ, Dept Epidemiol, Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN 46204 USA

[40] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA

[41] Mental Hlth Serv Copenhagen, Inst Biol Psychiat, Copenhagen, Denmark

[42] Copenhagen Univ Hosp, Danish Headache Ctr, Glostrup, Denmark

[43] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[44] Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland

[45] Eurac Res, Inst Biomed, Bolzano, Italy

[46] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA

[47] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[48] Broad Inst, Med & Populat Genet, Cambridge, MA USA

[49] Univ Med Ctr, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands

[50] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland

来源：

NATURE HUMAN BEHAVIOUR | 2021年 / 5卷 / 01期

基金：

英国医学研究理事会; 新加坡国家研究基金会; 英国惠康基金; 澳大利亚研究理事会; 芬兰科学院; 澳大利亚国家健康与医学研究理事会;

关键词：

LANGUAGE DOMINANCE; LINKAGE ANALYSIS; METAANALYSIS; MICROTUBULE; ASYMMETRY; AUTISM; LATERALIZATION; SCHIZOPHRENIA; ORIGINS; SCREEN;

D O I：

10.1038/s41562-020-00956-y

中图分类号：

B84 [心理学];

学科分类号：

04 ; 0402 ;

摘要：

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.

引用

页码：59 / 70

页数：14

共 50 条

[41] Genome-Wide Association Study Identifies Risk Loci for Cluster Headache
O'Connor, Emer
Fourier, Carmen
Ran, Caroline
Sivakumar, Prasanth
Liesecke, Franziska
Southgate, Laura
Harder, Aster V. E.
Vijfhuizen, Lisanne S.
Yip, Janice
Giffin, Nicola
Silver, Nicholas
Ahmed, Fayyaz
Hostettler, Isabel C.
Davies, Brendan
Cader, M. Zameel
Simpson, Benjamin S.
Sullivan, Roisin
Efthymiou, Stephanie
Adebimpe, Joycee
Quinn, Olivia
Campbell, Ciaran
Cavalleri, Gianpiero L.
Vikelis, Michail
Kelderman, Tim
Paemeleire, Koen
Kilbride, Emer
Grangeon, Lou
Lagrata, Susie
Danno, Daisuke
Trembath, Richard
Wood, Nicholas W.
Kockum, Ingrid
Winsvold, Bendik S.
Steinberg, Anna
Sjostrand, Christina
Waldenlind, Elisabet
Vandrovcova, Jana
Houlden, Henry
Matharu, Manjit
Belin, Andrea Carmine
ANNALS OF NEUROLOGY, 2021, 90 (02) : 193 - 202
[42] Genome-wide association study identifies a novel locus for cannabis dependence
Agrawal, A.
Chou, Y-L
Carey, C. E.
Baranger, D. A. A.
Zhang, B.
Sherva, R.
Wetherill, L.
Kapoor, M.
Wang, J-C
Bertelsen, S.
Anokhin, A. P.
Hesselbrock, V.
Kramer, J.
Lynskey, M. T.
Meyers, J. L.
Nurnberger, J. I.
Rice, J. P.
Tischfield, J.
Bierut, L. J.
Degenhardt, L.
Farrer, L. A.
Gelernter, J.
Hariri, A. R.
Heath, A. C.
Kranzler, H. R.
Madden, P. A. F.
Martin, N. G.
Montgomery, G. W.
Porjesz, B.
Wang, T.
Whitfield, J. B.
Edenberg, H. J.
Foroud, T.
Goate, A. M.
Bogdan, R.
Nelson, E. C.
MOLECULAR PSYCHIATRY, 2018, 23 (05) : 1293 - 1302
[43] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways (2018)
Howard, David M.
Adams, Mark J.
Shirali, Masoud
Clarke, Toni-Kim
Marioni, Riccardo E.
Davies, Gail
Coleman, Jonathan R. I.
Alloza, Clara
Shen, Xueyi
Barbu, Miruna C.
Wigmore, Eleanor M.
Gibson, Jude
Hagenaars, Saskia P.
Lewis, Cathryn M.
Ward, Joey
Smith, Daniel J.
Sullivan, Patrick F.
Haley, Chris S.
Breen, Gerome
Deary, Ian J.
McIntosh, Andrew M.
NATURE COMMUNICATIONS, 2018, 9 : 3578
[44] Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study
Hayden, Lystra P.
Cho, Michael H.
Raby, Benjamin A.
Beaty, Terri H.
Silverman, Edwin K.
Hersh, Craig P.
RESPIRATORY RESEARCH, 2018, 19
[45] Genome-Wide Association Study Reveals Two Nucleotide Variants Associated with Educational Attainment in Koreans
Ryu, J.
Lee, C.
RUSSIAN JOURNAL OF GENETICS, 2019, 55 (09) : 1130 - 1136
[46] Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume
Vojinovic, Dina
Adams, Hieab H.
Jian, Xueqiu
Yang, Qiong
Smith, Albert Vernon
Bis, Joshua C.
Teumer, Alexander
Scholz, Markus
Armstrong, Nicola J.
Hofer, Edith
Saba, Yasaman
Luciano, Michelle
Bernard, Manon
Trompet, Stella
Yang, Jingyun
Gillespie, Nathan A.
van der Lee, Sven J.
Neumann, Alexander
Ahmad, Shahzad
Andreassen, Ole A.
Ames, David
Amin, Najaf
Arfanakis, Konstantinos
Bastin, Mark E.
Becker, Diane M.
Beiser, Alexa S.
Beyer, Frauke
Brodaty, Henry
Bryan, R. Nick
Buelow, Robin
Dale, Anders M.
De Jager, Philip L.
Deary, Ian J.
DeCarli, Charles
Fleischman, Debra A.
Gottesman, Rebecca F.
van der Grond, Jeroen
Gudnason, Vilmundur
Harris, Tamara B.
Homuth, Georg
Knopman, David S.
Kwok, John B.
Lewis, Cora E.
Li, Shuo
Loeffler, Markus
Lopez, Oscar L.
Maillard, Pauline
El Marroun, Hanan
Mather, Karen A.
Mosley, Thomas H.
NATURE COMMUNICATIONS, 2018, 9
[47] Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants
Winsvold, Bendik S.
Bettella, Francesco
Witoelar, Aree
Anttila, Verneri
Gormley, Padhraig
Kurth, Tobias
Terwindt, Gisela M.
Freilinger, Tobias M.
Frei, Oleksander
Shadrin, Alexey
Wang, Yunpeng
Dale, Anders M.
van den Maagdenberg, Am M. J. M.
Chasman, Daniel I.
Nyholt, Dale R.
Palotie, Aarno
Andreassen, Ole A.
Zwart, John-Anker
PLOS ONE, 2017, 12 (09):
[48] Genome-Wide Association Study of Intracranial Aneurysm Identifies a New Association on Chromosome 7
Foroud, Tatiana
Lai, Dongbing
Koller, Daniel
van't Hof, Femke
Kurki, Mitja I.
Anderson, Craig S.
Brown, Robert D., Jr.
Connolly, Edward Sander
Eriksson, Johan G.
Flaherty, Matthew
Fornage, Myriam
von und zu Fraunberg, Mikael
Gaal, Emilia I.
Laakso, Aki
Hernesniemi, Juha
Huston, John
Jaaskelainen, Juha E.
Kiemeney, Lambertus A.
Kivisaari, Riku
Kleindorfer, Dawn
Ko, Nerissa
Lehto, Hanna
Mackey, Jason
Meissner, Irene
Moomaw, Charles J.
Mosley, Thomas H.
Moskala, Marek
Niemela, Mika
Palotie, Aarno
Pera, Joanna
Rinkel, Gabriel
Ripke, Stephan
Rouleau, Guy
Ruigrok, Ynte
Sauerbeck, Laura
Slowik, Agnieszka
Vermeulen, Sita H.
Woo, Daniel
Worrall, Bradford B.
Broderick, Joseph
STROKE, 2014, 45 (11) : 3194 - 3199
[49] The effect of genome-wide association scan quality control on imputation outcome for common variants
Southam, Lorraine
Panoutsopoulou, Kalliope
Rayner, N. William
Chapman, Kay
Durrant, Caroline
Ferreira, Teresa
Arden, Nigel
Carr, Andrew
Deloukas, Panos
Doherty, Michael
Loughlin, John
McCaskie, Andrew
Ollier, William E. R.
Ralston, Stuart
Spector, Timothy D.
Valdes, Ana M.
Wallis, Gillian A.
Wilkinson, J. Mark
Marchini, Jonathan
Zeggini, Eleftheria
EUROPEAN JOURNAL OF HUMAN GENETICS, 2011, 19 (05) : 610 - 614
[50] Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants
Malik, Rainer
Freilinger, Tobias
Anttila, Verneri
Vander Heiden, Jason
Traylor, Matthew
de Vries, Boukje
Holliday, Elizabeth G.
Terwindt, Gisela M.
Sturm, Jonathan
Bis, Joshua C.
Hopewell, Jemma C.
Ferrari, Michel D.
Rannikmae, Kristiina
Wessman, Maija
Kallela, Mikko
Kubisch, Christian
Fornage, Myriam
Meschia, James F.
Lehtimaki, Terho
Sudlow, Cathie
Clarke, Robert
Chasman, Daniel I.
Mitchell, Braxton D.
Maguire, Jane
Kaprio, Jaakko
Farrall, Martin
Raitakari, Olli T.
Kurth, Tobias
Ikram, M. Arfan
Reiner, Alex P.
Longstreth, W. T., Jr.
Rothwell, Peter M.
Strachan, David P.
Sharma, Pankaj
Seshadri, Sudha
Quaye, Lydia
Cherkas, Lynn
Schuerks, Markus
Rosand, Jonathan
Ligthart, Lannie
Boncoraglio, Giorgio B.
Smith, George Davey
van Duijn, Cornelia M.
Stefansson, Kari
Worrall, Bradford B.
Nyholt, Dale R.
Markus, Hugh S.
van den Maagdenberg, Arn M. J. M.
Cotsapas, Chris
Zwart, John A.
NEUROLOGY, 2015, 84 (21) : 2132 - 2145

← 1 2 3 4 5 →