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Investigating the Genetic Architecture of Noncognitive Skills using GWAS-by-Subtraction


Demange, Perline A; Malanchini, Margherita; Mallard, Travis T.; Biroli, Pietro; Cox, Simon R.; Grotzinger, Andrew D.; Tucker-Drob, Elliot M.; Abdellaoui, Abdel; Arseneault, Louise; & van Bergen, Elsje, et al. (2021). Investigating the Genetic Architecture of Noncognitive Skills using GWAS-by-Subtraction. Nature Genetics, 53(1), 35-44.


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.


Reference Type

Journal Article

Article Type


Year Published


Journal Title

Nature Genetics


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

Data Set/Study

Genome-wide association studies (GWASs)


United States of America