Replication Study of GWAS-Associated Variants in the <i>TUFM</i>, <i>SH2B1</i>, <i>ZNF638</i>, <i>NEGR1</i>, <i>ATP2A1</i>, <i>EXOC4</i>, and <i>CSE1L</i> Genes and Cognitive Abilities

Abstract

To date, a large number of genome-wide association analyses (GWAS) of cognitive abilities (i.e. intelligence, educational level, executive functions, etc.) have been conducted in European populations. A replication analysis of GWAS-associated variants of the general factor of intelligence in the development of spatial (3D) abilities in the individuals from Russia is relevant. In order to estimate the main effect of the most significant GWAS loci on spatial abilities in the Russian cohort (N = 1011, 18–25 years old) a set of seven “top” SNPs (p 10–13) was formed: TUFM rs7187776, SH2B1 rs7198606, ZNF638 rs2287326, NEGR1 rs12128707, ATP2A1 rs8055138, EXOC4 rs1362739, and CSE1L rs6063353. Statistically significant differences (р 0.05) in genotype frequencies distribution of ATP2A1 rs8055138, NEGR1 rs12128707, and ZNF638 rs2287326 between Russians, Tatars, and Udmurts have been observed. As a result of analysis of genotype-by-environment interactions we revealed ethnicity-specific character of associations: in Russians maternal age at delivery (βST = 0.84, p = 0.005) and in Tatars bilingual/unilingual rearing (βST = 0.44, р = 0.020) modulated association of ZNF638 rs2287326 with spatial abilities. Moreover, urban/rural residency in childhood modulated association of TUFM rs7187776 with 3D abilities (βST = 0.41, р = 0.009). The data obtained indicate the involvement of the ZNF638, TUFM, SH2B1, and EXOC4 genes, which are responsible for adipogenesis, in the manifestation of cognitive abilities, and, therefore, confirms the relationship between cognitive and metabolic disorders. Nevertheless, ethnicity-specific character of demonstrated associations and differences in genotype frequencies of analyzed GWAS-SNPs point to the specific pattern of associated genetic loci characteristic for the Russian cohort and to the complexity of replication of data reported for the combined samples of Europeans.