A Genome-Wide Association Study Identifies Genetic Variants Associated with Mathematics Ability

Abstract

Mathematics ability is a complex cognitive trait with polygenic heritability. Genome-wide association study (GWAS) has been an effective approach to investigate genetic components underlying mathematic ability. Although previous studies reported several candidate genetic variants, none of them exceeded genome-wide significant threshold in general populations. Herein, we performed GWAS in Chinese elementary school students to identify potential genetic variants associated with mathematics ability. The discovery stage included 494 and 504 individuals from two independent cohorts respectively. The replication stage included another cohort of 599 individuals. In total, 28 of 81 candidate SNPs that met validation criteria were further replicated. Combined meta-analysis of three cohorts identified four SNPs (rs1012694, rs11743006, rs17778739 and rs17777541) of SPOCK1 gene showing association with mathematics ability (minimum p value 5.67 × 10−10, maximum β −2.43). The SPOCK1 gene is located on chromosome 5q31.2 and encodes a highly conserved glycoprotein testican-1 which was associated with tumor progression and prognosis as well as neurogenesis. This is the first study to report genome-wide significant association of individual SNPs with mathematics ability in general populations. Our preliminary results further supported the role of SPOCK1 during neurodevelopment. The genetic complexities underlying mathematics ability might contribute to explain the basis of human cognition and intelligence at genetic level.

Gene–Environment Interplay and Individual Differences in Behavior

“…However, the "phenotype" educational attainment has been operationally defined in many different ways, such as years of education (Okbay et al, 2016), highest degree completed (Belsky et al, 2016), and score on a U.K. nationwide examination (Rimfeld et al, 2015;Shakeshaft et al, 2013). It is also possible to study the link between genetics and certain components of education attainment such as mathematics (Chen et al, 2017;Wang et al, 2014) or reading (Christopher et al, 2016;Davis et al, 2014;Gialluisi, Guadalupe, Francks, & Fisher, 2016). It is unclear whether these different measurements of educational attainment are all tapping into the same phenotype, or instead measuring distinct components of behavior.…”

Cognitive genomics: Searching for the genetic roots of neuropsychological functioning.

“…Davis and colleagues (2014) found several trend-level associations with mathematical abilities in this study, but again none reached genome-wide significance (Davis et al, 2014). Recently, in a combined meta-analysis of 3 cohorts of Chinese elementary school students, Chen and colleagues (2017) identified the first genome-wide significant SNPs associated with mathematical ability. In particular, they identified four intronic SNPs in the SPOCK1 gene, which has been implicated in various types of cancer and may play a key role during neurogenesis.…”

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

“…However, such analyses have not been possible so far, as the existing GWASs of school grades were based on small sample sizes and hence were not statistically powerful enough to study the genetic overlap with the psychiatric disorder. [20][21][22][23] Here we present the largest GWAS of school grades to date disentangling the polygenic architecture of various domains of school performance and their complex phenotypic and genetic relationships with six major psychiatric disorders (ADHD, ASD, SCZ, BD, major depressive disorder (MDD) and AN). The overall study design is shown in Supplementary Fig.…”