Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction

Perline A. Demange, Margherita Malanchini, Travis T. Mallard, Pietro Biroli, Simon R. Cox, Andrew D. Grotzinger, Elliot M. Tucker-drob, Abdel Abdellaoui, Louise Arseneault, Elsje Van Bergen, Dorret I. Boomsma, Avshalom Caspi, David L. Corcoran, Benjamin W. Domingue, Kathleen Mullan Harris, Hill F. Ip, Colter Mitchell, Terrie E. Moffitt, Richie Poulton, Joseph A. PrinzKaren Sugden, Jasmin Wertz, Benjamin S. Williams, Eveline L. De Zeeuw, Daniel W. Belsky, K. Paige Harden, Michel G. Nivard

Research output: Contribution to journalArticlepeer-review

Abstract

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.
Original languageEnglish
Pages (from-to)35-44
Number of pages16
JournalNature Genetics
Volume53
Issue number1
Early online date7 Jan 2021
DOIs
Publication statusPublished - Jan 2021

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