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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 (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.

SUBMITTER: Cuellar-Partida G

PROVIDER: S-EPMC7116623 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Cuellar-Partida Gabriel G Tung Joyce Y JY Eriksson Nicholas N Albrecht Eva E Aliev Fazil F Andreassen Ole A OA Barroso Inês I Beckmann Jacques S JS Boks Marco P MP Boomsma Dorret I DI Boyd Heather A HA Breteler Monique M B MMB Campbell Harry H Chasman Daniel I DI Cherkas Lynn F LF Davies Gail G de Geus Eco J C EJC Deary Ian J IJ Deloukas Panos P Dick Danielle M DM Duffy David L DL Eriksson Johan G JG Esko Tõnu T Feenstra Bjarke B Geller Frank F Gieger Christian C Giegling Ina I Gordon Scott D SD Han Jiali J Hansen Thomas F TF Hartmann Annette M AM Hayward Caroline C Heikkilä Kauko K Hicks Andrew A AA Hirschhorn Joel N JN Hottenga Jouke-Jan JJ Huffman Jennifer E JE Hwang Liang-Dar LD Ikram M Arfan MA Kaprio Jaakko J Kemp John P JP Khaw Kay-Tee KT Klopp Norman N Konte Bettina B Kutalik Zoltan Z Lahti Jari J Li Xin X Li Xin X Loos Ruth J F RJF Luciano Michelle M Magnusson Sigurdur H SH Mangino Massimo M Marques-Vidal Pedro P Martin Nicholas G NG McArdle Wendy L WL McCarthy Mark I MI Medina-Gomez Carolina C Melbye Mads M Melville Scott A SA Metspalu Andres A Milani Lili L Mooser Vincent V Nelis Mari M Nyholt Dale R DR O'Connell Kevin S KS Ophoff Roel A RA Palmer Cameron C Palotie Aarno A Palviainen Teemu T Pare Guillaume G Paternoster Lavinia L Peltonen Leena L Penninx Brenda W J H BWJH Polasek Ozren O Pramstaller Peter P PP Prokopenko Inga I Raikkonen Katri K Ripatti Samuli S Rivadeneira Fernando F Rudan Igor I Rujescu Dan D Smit Johannes H JH Smith George Davey GD Smoller Jordan W JW Soranzo Nicole N Spector Tim D TD Pourcain Beate St BS Starr John M JM Stefánsson Hreinn H Steinberg Stacy S Teder-Laving Maris M Thorleifsson Gudmar G Stefánsson Kári K Timpson Nicholas J NJ Uitterlinden André G AG van Duijn Cornelia M CM van Rooij Frank J A FJA Vink Jaqueline M JM Vollenweider Peter P Vuoksimaa Eero E Waeber Gérard G Wareham Nicholas J NJ Warrington Nicole N Waterworth Dawn D Werge Thomas T Wichmann H-Erich HE Widen Elisabeth E Willemsen Gonneke G Wright Alan F AF Wright Margaret J MJ Xu Mousheng M Zhao Jing Hua JH Kraft Peter P Hinds David A DA Lindgren Cecilia M CM Mägi Reedik R Neale Benjamin M BM Evans David M DM Medland Sarah E SE

Nature human behaviour 20200928 1

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<sup>-8</sup>) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the ae ...[more]

PMID: 32989287

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Project description:A rotator cuff is a muscle and tendon surrounding the shoulder joint, and a rotator cuff tear can be caused by overuse or injury, which leads to great pain in affected individuals. However, rotator cuff tear is a multifactorial process whose underlying mechanism is still unclear. Many previous studies have suggested an important role of genetic predisposition, such as single-nucleotide polymorphisms (SNPs), in explaining the genesis of tendinopathy. This study aimed to identify specific genes or genetic variants associated with rotator cuff tears by performing a genome-wide association study (GWAS) using an independent case of rotator cuff tears. GWAS was performed using data from CHA Bundang Medical Center with 20 cases of rotator cuff tears, and 20 cases of healthy controls genotyped on the Illumina HiSeq 2500. Tests of association were performed using the Burrows−Wheeler Aligner (BWA) software at 284,246 SNPs. Data were filtered based on sequence ontology, minor allele frequency, and Hardy−Weinberg equilibrium values, and SNPs were considered significant if the p-value was <0.05. The tests of association revealed more than 20 significantly associated SNPs. SNPs showing the highest significance occurred in candidate genes, including LAIR2 (rs2287828, OR 9.116, p-value 5.49 × 10−4) on chromosome 19 and CRIPAK (rs9328733, OR 6, p-value 1.11 × 10−3) and REST (rs2228991, OR 8.222, p-value 1.20 × 10−3) on chromosome 4. This study attempted to identify genetic variants influencing rotator cuff tears through a genome-wide association study using a dense set of SNPs. More than 20 SNPs were significantly associated with rotator cuff tears. The major limitation of this study is that it was conducted on a small study group and requires further validation. Nevertheless, the identification of potential genetic variants related to rotator cuff injury would aid in the early detection of individuals at risk for the development of tendinopathy and will provide insight into future gene therapies.

Dataset Information

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

Publications

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

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