Common genetic variants associated with cognitive performance identified using the proxy-phenotype method
Rietveld CA., Esko T., Davies G., Pers TH., Turley P., Benyamin B., Chabris CF., Emilsson V., Johnson AD., Lee JJ., Leeuw CD., Marioni RE., Medland SE., Miller MB., Rostapshova O., van der Lee SJ., Vinkhuyzen AAE., Amin N., Conley D., Derringer J., van Duijn CM., Fehrmann R., Franke L., Glaeser EL., Hansell NK., Hayward C., Iacono WG., Ibrahim-Verbaas C., Jaddoe V., Karjalainen J., Laibson D., Lichtenstein P., Liewald DC., Magnusson PKE., Martin NG., McGue M., McMahon G., Pedersen NL., Pinker S., Porteous DJ., Posthuma D., Rivadeneira F., Smith BH., Starr JM., Tiemeier H., Timpson NJ., Trzaskowski M., Uitterlinden AG., Verhulst FC., Ward ME., Wright MJ., Davey Smith G., Deary IJ., Johannesson M., Plomin R., Visscher PM., Benjamin DJ., Cesarini D., Koellinger PD.
Significance We identify several common genetic variants associated with cognitive performance using a two-stage approach: we conduct a genome-wide association study of educational attainment to generate a set of candidates, and then we estimate the association of these variants with cognitive performance. In older Americans, we find that these variants are jointly associated with cognitive health. Bioinformatics analyses implicate a set of genes that is associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory. In addition to the substantive contribution, this work also serves to show a proxy-phenotype approach to discovering common genetic variants that is likely to be useful for many phenotypes of interest to social scientists (such as personality traits).