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Genome-wide association study identifies 48 common genetic variants associated with handedness
Nature Human Behaviour ( IF 21.4 ) Pub Date : 2020-09-28 , DOI: 10.1038/s41562-020-00956-y
Gabriel Cuellar-Partida 1, 2 , Joyce Y Tung 2 , Nicholas Eriksson 2 , Eva Albrecht 3 , Fazil Aliev 4, 5 , Ole A Andreassen 6, 7 , Inês Barroso 8, 9, 10 , Jacques S Beckmann 11 , Marco P Boks 12 , Dorret I Boomsma 13, 14 , Heather A Boyd 15 , Monique M B Breteler 16 , Harry Campbell 17 , Daniel I Chasman 18, 19 , Lynn F Cherkas 20 , Gail Davies 21, 22 , Eco J C de Geus 13, 14 , Ian J Deary 21, 22 , Panos Deloukas 23 , Danielle M Dick 4, 24 , David L Duffy 25 , Johan G Eriksson 26, 27, 28, 29 , Tõnu Esko 30, 31 , Bjarke Feenstra 15 , Frank Geller 15 , Christian Gieger 32, 33 , Ina Giegling 34 , Scott D Gordon 25 , Jiali Han 35, 36 , Thomas F Hansen 37, 38 , Annette M Hartmann 34 , Caroline Hayward 39 , Kauko Heikkilä 40 , Andrew A Hicks 41 , Joel N Hirschhorn 42, 43, 44 , Jouke-Jan Hottenga 13, 14 , Jennifer E Huffman 39 , Liang-Dar Hwang 1 , M Arfan Ikram 45 , Jaakko Kaprio 40, 46 , John P Kemp 1, 47 , Kay-Tee Khaw 48 , Norman Klopp 49 , Bettina Konte 34 , Zoltan Kutalik 50, 51 , Jari Lahti 52, 53, 54 , Xin Li 35, 36 , Ruth J F Loos 9, 55, 56 , Michelle Luciano 21, 22 , Sigurdur H Magnusson 57 , Massimo Mangino 20 , Pedro Marques-Vidal 58 , Nicholas G Martin 25 , Wendy L McArdle 59 , Mark I McCarthy 60, 61, 62, 63 , Carolina Medina-Gomez 45, 64 , Mads Melbye 15, 65, 66 , Scott A Melville 41 , Andres Metspalu 30 , Lili Milani 30 , Vincent Mooser 67 , Mari Nelis 30 , Dale R Nyholt 25, 68 , Kevin S O'Connell 6 , Roel A Ophoff 69, 70, 71 , Cameron Palmer 72 , Aarno Palotie 40 , Teemu Palviainen 40 , Guillaume Pare 73 , Lavinia Paternoster 74 , Leena Peltonen 75 , Brenda W J H Penninx 14, 76 , Ozren Polasek 77, 78 , Peter P Pramstaller 41 , Inga Prokopenko 79, 80 , Katri Raikkonen 52 , Samuli Ripatti 40 , Fernando Rivadeneira 45, 64 , Igor Rudan 81 , Dan Rujescu 34 , Johannes H Smit 14, 76 , George Davey Smith 74 , Jordan W Smoller 82, 83 , Nicole Soranzo 8 , Tim D Spector 20 , Beate St Pourcain 74, 84, 85 , John M Starr 86, 87 , Hreinn Stefánsson 57 , Stacy Steinberg 57 , Maris Teder-Laving 30 , Gudmar Thorleifsson 57 , Kári Stefánsson 57 , Nicholas J Timpson 74 , André G Uitterlinden 45, 64 , Cornelia M van Duijn 45, 64 , Frank J A van Rooij 45 , Jaqueline M Vink 13, 88 , Peter Vollenweider 58 , Eero Vuoksimaa 40 , Gérard Waeber 58 , Nicholas J Wareham 9 , Nicole Warrington 1 , Dawn Waterworth 89 , Thomas Werge 37, 65, 90 , H-Erich Wichmann 91 , Elisabeth Widen 40 , Gonneke Willemsen 13 , Alan F Wright 39 , Margaret J Wright 92, 93 , Mousheng Xu 94 , Jing Hua Zhao 95 , Peter Kraft 94 , David A Hinds 2 , Cecilia M Lindgren 60, 96 , Reedik Mägi 30 , Benjamin M Neale 31, 97 , David M Evans 1, 74 , Sarah E Medland 1, 98
Affiliation  

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.



中文翻译:


全基因组关联研究确定了与惯用手相关的 48 种常见遗传变异



由于惯用手与语言的关系以及左撇子在某些神经发育障碍中的比例过高,因此已被广泛研究。利用来自英国生物银行、23andMe 和国际惯用手协会的数据,我们对惯用手进行了全基因组关联荟萃分析 ( N = 1,766,671)。我们发现 41 个基因座( P < 5 × 10 -8 )与左利手相关,7 个与双手灵巧相关。组织富集分析表明中枢神经系统与惯用手的病因有关。还强调了包括微管和大脑形态调节在内的途径。我们发现左利手与神经精神特征(包括精神分裂症和双相情感障碍)之间存在暗示性的正遗传相关性。此外,左撇子和双手灵巧之间的遗传相关性较低( r G = 0.26),这意味着这些特征在很大程度上受到不同遗传机制的影响。我们的研究结果表明,惯用手是高度多基因的,而易患左撇子的基因变异可能是与某些精神疾病相关的部分原因。

更新日期:2020-09-28
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