Genome-wide association study of school grades identifies a genetic overlap between language ability, psychopathology and creativity

Abstract

Individuals with psychiatric disorders perform differently in school compared to the general population. Genetic factors contribute substantially to such differences. It is however unclear if differential performance is seen across all cognitive domains such as math and language. Here we report a genome-wide association study (GWAS) of school grades in 30,982 individuals (18,495 with and 12,487 without one or more of six major psychiatric disorders) and a replication study in 4,547 individuals. GWAS of overall school performance yielded results that were highly similar to the results of a previous GWAS of educational attainment. Analyzing subject specific grades, we observed that math performance was severely affected whereas language performance (Danish and English) was relatively unaffected or enhanced in those with psychiatric disorders compared to controls. We found that the genetic variants associated with poor math performance, but better language performance were also associated with increased risk for multiple psychiatric disorders. The same variants were also associated with creativity, which we show through a polygenic score analysis of 2953 creative professionals and 164,622 controls. The results overall suggest that risk for psychiatric disorders, language ability and creativity might have overlapping genetic roots.

Polygenic prediction of school performance in children with and without psychiatric disorders

“…All the six grades that we analyzed were strongly correlated with each other suggesting that those who performed well in one subject performed well in others as well 19 ( Supplementary Fig. 1).…”

“…Our study individuals comprised of 18,495 with one or more of six major psychiatric disorders (ADHD=5,238, ASD=3,859, SCZ=1,356, MDD=9,719, BPD=839 and AN=1,680) and 12,487 without any of these six disorders 19 (Table 1). We assessed the school performance based on six different school grades (Danish written, oral and grammar, English oral, and mathematics written and oral, or problem solving with and without aids; Methods).…”

“…Yet their school performance differed significantly from the controls, which we have reported previously. 19 Hence, we considered everyone with a psychiatric diagnosis in the register (as of Dec 2016) as cases irrespective of when they received their diagnoses. The sample characteristics within each disorder group and controls are summarized in Table 1.…”

“…This is equivalent to extracting a general cognitive ability factor (g) from a PCA of multiple cognitive test scores. 27 We have previously reported the genetic architecture of E1 by performing a genome-wide association study (GWAS) and showed that there is an almost complete genetic overlap between E1 and EA 19 (r g =0.90; SE=0.01; P=4.8x10 −198 ). Hence, here we used E1 as a proxy phenotype for EA and studied its association with EA-PGS across the six psychiatric disorder groups and controls.…”

“…16 Individuals with-or those at risk for-psychiatric disorders often score lower than individuals without psychiatric disorders in school. 17,18 Although genetic factors related to cognition partly explain this association, 19 other factors such as family socioeconomic status (SES) might contribute to this association as well, for example, individuals with psychiatric disorders such as schizophrenia and ADHD often have low SES compared to general population. [20][21][22] Additionally, there is a significant sharing of genetic risk variants between psychiatric disorders and cognitive phenotypes such as EA 23 and intelligence.…”