Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

Perline Demange; Margherita Malanchini; Travis T. Mallard; Pietro Biroli; Simon R. Cox; Andrew David Grotzinger; Elliot M. Tucker–Drob; Abdel Abdellaoui; Louise Arseneault; Elsje van Bergen; Dorret Irene Boomsma; Avshalom Caspi; David L. Corcoran; Benjamin W. Domingue; Kathleen Mullan Harris; Hill Fung Ip; Colter M. Mitchell; Terrie E. Moffitt; Richie Poulton; Joseph A. Prinz; Karen Sugden; Jasmin Wertz; Benjamin S. Williams; Eveline L. de Zeeuw; Daniel W. Belsky; K. Paige Harden; Michel Guillaume Nivard

doi:10.1038/s41588-020-00754-2

GeneticsNature GeneticsJan 1, 2021

Peer-reviewed journal article

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

Perline Demange iD, Margherita Malanchini iD, Travis T. Mallard iD, Pietro Biroli iD, Simon R. Cox iD, Andrew David Grotzinger iD, Elliot M. Tucker–Drob iD, Abdel Abdellaoui iD, Louise Arseneault iD, Elsje van Bergen iD, Dorret Irene Boomsma iD, Avshalom Caspi iD, David L. Corcoran iD, Benjamin W. Domingue iD, Kathleen Mullan Harris iD, Hill Fung Ip iD, Colter M. Mitchell iD, Terrie E. Moffitt iD, Richie Poulton iD, Joseph A. Prinz, Karen Sugden iD, Jasmin Wertz iD, Benjamin S. Williams iD, Eveline L. de Zeeuw iD, Daniel W. Belsky iD, , Michel Guillaume Nivard iD

Abstract

Educational attainment (EA) is influenced by cognitive abilities and by other characteristics and traits. However little is known about the genetic architecture of these "non-cognitive" contributions to EA. Here, we use Genomic Structural Equation Modelling and results of prior genome-wide association studies (GWASs) of EA (N = 1,131,881) and cognitive test performance (N = 257,841) to estimate SNP associations with variation in EA that is independent of cognitive ability. We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in EA. Phenotypic and biological annotation revealed that (1) both cognitive and non-cognitive contributions to EA were genetically correlated with socioeconomic success and longevity; and (2) non-cognitive contributions to EA were related to personality, decision making, risk-behavior, and increased risk for psychiatric disorders; (3) non-cognitive and cognitive contributions to EA were enriched in the same tissues and cell types, but (4) showed different associations with gray-matter neuroimaging phenotypes.

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