Familial environment modifies association of DNA methyltransferases gene variants and cognitive functioningстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 8 сентября 2021 г.
Аннотация:The study of cognitive functioning and cognitive deficitis becoming increasingly relevant today due to an increased frequency of cognitive decline and neurodegenerative disorders even in middle age. In turn, the level of cognitive functioning is the basis of life success and individual self-realization. It is established that the mechanisms underlying individual predisposition to individual cognitive functioning are complex, and genetic, epigenetic and environmental factors play a significant role. Together with thedata on associated SNPs[1], recent findings point to a significant role of epigenetic mechanisms in cognitive development. Since environmental factors [2] and DNA methyltransferases are responsible for certain epigenetic changes in DNAmethylationprofile[3],the present study aimed toexamine the main effect of DNA methyltransferases gene(DNMT1, DNMT3A, DNMT3B) variants on cognitive abilities and to detect gene-by-environment interaction models explaining individual variance in cognitive functioning in mentally healthy young adults from Russia. The study consisted of 897 mentally healthy individuals (79% women;19.74±1.51years) of Caucasian origin(428 Russians, 200 Tatars, 117 Udmurts, and 152 of mixed ethnicity) from Russia.The assessment of cognitive abilities (“number sense”, 3D mental rotation, non-verbal intelligence,working memory) was performed using the Battery of cognitive tests developed at International Laboratory for Interdisciplinary Investigations into Individual Differencesin Learning(InLab)(Department of Psychology, Goldsmiths, University of London).The genotyping of DNMT1rs10418707, DNMT3Ars1550117, DNMT3Brs2424932 gene SNPs was performed via PCR-based KASP genotyping technology on“CFX96” DNAAnalyzer(BioRad, USA).Statistical analysis included multiple linear regression followed by FDR-correction for multiple testing (PLINK v.1.09). Genotypes and 13 environmental parameters served as independent factors and cognitive abilities as dependentvariable.We failed to observe the main effect of examined gene variants in individual differences in cognitive functioning after correction for multiple comparisons. However, the GxEanalysis revealed statistically significant models,which explained individual variances in the level of non-verbal intelligence:1)DNMT1rs10418707andrearinginbilingualfamily (β=4.28; Р=0.003);2)DNMT3Ars1550117 and increased family income in childhood(β=16.7; Р=0.008);3)DNMT3B rs2424932 and rearing in a full family(β=-4.61; Р=0.023); 4) DNMT3Brs2424932 and paternal age at child’s birth(β=-0.13; Р=0.037).In turn, the income level modulated the association of DNMT1rs10418707(β=-2.34; Р=0.017)and DNMT3B rs2424932(β=-1.75;Р=0.025)with workingmemory, which is impaired in neurodegenerative diseasesassociated with cognitive decline.Our findings indicate a significant role of interaction between rearing specificity(including family income in childhood,bilingual rearing and the involvement of both parentsinindividual’s development) and genetic predisposition mediated by variants in the genes responsible for the changes in DNA methylation profile in cognitive functioning.