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

被引：99

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

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 69 条

[31] Efficient Bayesian mixed-model analysis increases association power in large cohorts [J].

Loh, Po-Ru ;

Tucker, George ;

Bulik-Sullivan, Brendan K. ;

Vilhjalmsson, Bjarni J. ;

Finucane, Hilary K. ;

Salem, Rany M. ;

Chasman, Daniel I. ;

Ridker, Paul M. ;

Neale, Benjamin M. ;

Berger, Bonnie ;

Patterson, Nick ;

Price, Alkes L. .

NATURE GENETICS, 2015, 47 (03) :284-+

[32] The Genotype-Tissue Expression (GTEx) project [J].

Lonsdale, John ;

Thomas, Jeffrey ;

Salvatore, Mike ;

Phillips, Rebecca ;

Lo, Edmund ;

Shad, Saboor ;

Hasz, Richard ;

Walters, Gary ;

Garcia, Fernando ;

Young, Nancy ;

Foster, Barbara ;

Moser, Mike ;

Karasik, Ellen ;

Gillard, Bryan ;

Ramsey, Kimberley ;

Sullivan, Susan ;

Bridge, Jason ;

Magazine, Harold ;

Syron, John ;

Fleming, Johnelle ;

Siminoff, Laura ;

Traino, Heather ;

Mosavel, Maghboeba ;

Barker, Laura ;

Jewell, Scott ;

Rohrer, Dan ;

Maxim, Dan ;

Filkins, Dana ;

Harbach, Philip ;

Cortadillo, Eddie ;

Berghuis, Bree ;

Turner, Lisa ;

Hudson, Eric ;

Feenstra, Kristin ;

Sobin, Leslie ;

Robb, James ;

Branton, Phillip ;

Korzeniewski, Greg ;

Shive, Charles ;

Tabor, David ;

Qi, Liqun ;

Groch, Kevin ;

Nampally, Sreenath ;

Buia, Steve ;

Zimmerman, Angela ;

Smith, Anna ;

Burges, Robin ;

Robinson, Karna ;

Valentino, Kim ;

Bradbury, Deborah .

NATURE GENETICS, 2013, 45 (06) :580-585

[33] Robust relationship inference in genome-wide association studies [J].

Manichaikul, Ani ;

Mychaleckyj, Josyf C. ;

Rich, Stephen S. ;

Daly, Kathy ;

Sale, Michele ;

Chen, Wei-Min .

BIOINFORMATICS, 2010, 26 (22) :2867-2873

[34] Microtubule and microtubule associated protein anomalies in psychiatric disease [J].

Marchisella, Francesca ;

Coffey, Eleanor T. ;

Hollos, Patrik .

CYTOSKELETON, 2016, 73 (10) :596-611

[35] HANDEDNESS, LANGUAGE DOMINANCE AND APHASIA - A GENETIC MODEL [J].

MCMANUS, IC .

PSYCHOLOGICAL MEDICINE, 1985, :1-+

[36] Handedness in twins: Joint analysis of data from 35 samples [J].

Medland, SE ;

Duffy, DL ;

Wright, MJ ;

Geffen, GM ;

Martin, NG .

TWIN RESEARCH AND HUMAN GENETICS, 2006, 9 (01) :46-53

[37] Opposite effects of androgen receptor CAG repeat length on increased risk of left-handedness in males and females [J].

Medland, SE ;

Duffy, DL ;

Spurdle, AB ;

Wright, MJ ;

Geffen, GM ;

Montgomery, GW ;

Martin, NG .

BEHAVIOR GENETICS, 2005, 35 (06) :735-744

[38]

Michael Macpherson J., 2014, BIORXIV, DOI [10.1101/010512, DOI 10.1101/010512]

[39] OpenMx 2.0: Extended Structural Equation and Statistical Modeling [J].

Neale, Michael C. ;

Hunter, Michael D. ;

Pritikin, Joshua N. ;

Zahery, Mahsa ;

Brick, Timothy R. ;

Kirkpatrick, Robert M. ;

Estabrook, Ryne ;

Bates, Timothy C. ;

Maes, Hermine H. ;

Boker, Steven M. .

PSYCHOMETRIKA, 2016, 81 (02) :535-549

[40] An xQTL map integrates the genetic architecture of the human brain's transcriptome and epigenome [J].

Ng, Bernard ;

White, Charles C. ;

Klein, Hans-Ulrich ;

Sieberts, Solveig K. ;

McCabe, Cristin ;

Patrick, Ellis ;

Xu, Jishu ;

Yu, Lei ;

Gaiteri, Chris ;

Bennett, David A. ;

Mostafavi, Sara ;

De Jager, Philip L. .

NATURE NEUROSCIENCE, 2017, 20 (10) :1418-+

← 1 2 3 4 5 6 7 →