| Autor: |
Cherbuin N; National Centre for Epidemiology and Population Health, Australian National University, Canberra 2601, Australia., Patel H; John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia., Walsh EI; National Centre for Epidemiology and Population Health, Australian National University, Canberra 2601, Australia., Ambikairajah A; National Centre for Epidemiology and Population Health, Australian National University, Canberra 2601, Australia.; Discipline of Psychology, University of Canberra, Canberra 2617, Australia.; Centre for Ageing Research and Translation, Faculty of Health, University of Canberra, Canberra 2617, Australia., Burns R; National Centre for Epidemiology and Population Health, Australian National University, Canberra 2601, Australia., Brüstle A; John Curtin School of Medical Research, Australian National University, Canberra 2601, Australia., Rasmussen LJ; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark. |
| Abstrakt: |
Several modifiable risk factors for neurodegeneration and dementia have been identified, although individuals vary in their vulnerability despite a similar risk of exposure. This difference in vulnerability could be explained at least in part by the variability in DNA repair mechanisms' efficiency between individuals. Therefore, the aim of this study was to test associations between documented, prevalent genetic variation (single nucleotide polymorphism, SNP) in DNA repair genes, cognitive function, and brain structure. Community-living participants ( n = 488,159; 56.54 years (8.09); 54.2% female) taking part in the UK Biobank study and for whom cognitive and genetic measures were available were included. SNPs in base excision repair (BER) genes of the bifunctional DNA glycosylases OGG1 (rs1052133, rs104893751), NEIL1 (rs7402844, rs5745906), NEIL2 (rs6601606), NEIL3 (rs10013040, rs13112390, rs13112358, rs1395479), MUTYH (rs34612342, rs200165598), NTHL1 (rs150766139, rs2516739) were considered. Cognitive measures included fluid intelligence, the symbol-digit matching task, visual matching, and trail-making. Hierarchical regression and latent class analyses were used to test the associations between SNPs and cognitive measures. Associations between SNPs and brain measures were also tested in a subset of 39,060 participants. Statistically significant associations with cognition were detected for 12 out of the 13 SNPs analyzed. The strongest effects amounted to a 1-6% difference in cognitive function detected for NEIL1 (rs7402844), NEIL2 (rs6601606), and NTHL1 (rs2516739). Associations varied by age and sex, with stronger effects detected in middle-aged women. Weaker associations with brain measures were also detected. Variability in some BER genes is associated with cognitive function and brain structure and may explain variability in the risk for neurodegeneration and dementia. |
