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

Demange, P. A.; Malanchini, M.; Mallard, T. T.; Biroli, P.; Cox, S. R.; Grotzinger, A. D.; Tucker-Drob, E. M.; Abdellaoui, A.; Arseneault, L.; Caspi, A.; Corcoran, D.; Domingue, B.; Mitchell, C.; van Bergen, E.; Boomsma, D. I.; Harris, K. M.; Ip, H. F.; Moffitt, T. E.; Poulton, R.; Prinz, J.; Sugden, K.; Wertz, J.; Williams, B.; de Zeeuw, E. L.; Belsky, D. W.; Harden, K. P.; Nivard, M. G.

doi:10.1101/2020.01.14.905794

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bioRxiv · 10.1101/2020.01.14.905794

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

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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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Demange, P. A., Malanchini, M., Mallard, T. T., Biroli, P., Cox, S. R., Grotzinger, A. D., Tucker-Drob, E. M., Abdellaoui, A., Arseneault, L., Caspi, A., Corcoran, D., Domingue, B., Mitchell, C., van Bergen, E., Boomsma, D. I., Harris, K. M., Ip, H. F., Moffitt, T. E., Poulton, R., Prinz, J., Sugden, K., Wertz, J., Williams, B., de Zeeuw, E. L., Belsky, D. W., Harden, K. P., Nivard, M. G.. 2020-01-15. Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction. https://doi.org/10.1101/2020.01.14.905794

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