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

• Published in: Russian journal of genetics 2023-09, Vol.59 (9), p.940-948
• Main Authors: Kazantseva, A. V., Davydova, Yu. D., Enikeeva, R. F., Takhirova, Z. R., Mustafin, R. N., Lobaskova, M. M., Malykh, S. B., Khusnutdinova, E. K.
• Format: Article
• Language: English
• Subjects: adipogenesis; Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; childhood; cognition; educational status; frequency distribution; genotype; genotype-environment interaction; Human Genetics; Microbial Genetics and Genomics; Russia
• ISSN: 1022-7954; 1608-3369
• DOI: 10.1134/S1022795423090065

A large number of genome-wide association studies (GWASs) 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 effects 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 the genotype frequency 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 the ethnicity-specific character of associations: in Russians maternal age at delivery (β ST = 0.84, p = 0.005) and in Tatars bilingual/unilingual rearing (β ST = 0.44, р = 0.020) modulated association of ZNF638 rs2287326 with spatial abilities. Moreover, urban/rural residency in childhood modulated the association of TUFM rs7187776 with 3D abilities (β ST = 0.41, р = 0.009). The data we obtained indicate the involvement of the ZNF638 , TUFM , SH2B1 , and EXOC4 genes, which are related to adipogenesis, in the manifestation of cognitive abilities, and, therefore, confirms the relationship between cognitive and metabolic disorders. Nevertheless, the 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.