Genome-wide association study identifies 48 common genetic variants associated with handedness.
Cuellar-Partida G., Tung JY., Eriksson N., Albrecht E., Aliev F., Andreassen OA., Barroso I., Beckmann JS., Boks MP., Boomsma DI., Boyd HA., Breteler MMB., Campbell H., Chasman DI., Cherkas LF., Davies G., de Geus EJC., 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 J-J., Huffman JE., Hwang L-D., Ikram MA., Kaprio J., Kemp JP., Khaw K-T., Klopp N., Konte B., Kutalik Z., Lahti J., Li X., Loos RJF., Luciano M., Magnusson SH., Mangino M., Marques-Vidal P., Martin NG., McArdle WL., McCarthy MI., Medina-Gomez C., Melbye M., Melville SA., Metspalu A., Milani L., Mooser V., Nelis M., Nyholt DR., O'Connell KS., Ophoff RA., 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 AG., van Duijn CM., van Rooij FJA., Vink JM., Vollenweider P., Vuoksimaa E., Waeber G., Wareham NJ., Warrington N., Waterworth D., Werge T., Wichmann H-E., 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.
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.