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• W4387496765 abstract "Cognition is a complex construct influenced by genetic predisposition, environmental factors, and their interplay. Although twin studies have revealed substantial heritability of cognitive function (0.33 to 0.80), the influence of genetic susceptibility on cognition under different environmental conditions remains unclear. However, most studies have a limited inclusion of genetic and environmental factors, constraining a thorough exploration. In this study, we aimed to investigate the effects of polygenic risk scores (PGSs) on cognitive domains while accounting for environmental influences, as measured by the LIfestyle for BRAin health index (LIBRA), comprising established risk factors for cognitive decline. We examined the associations between genetic predispositions to mental health, neurodevelopmental disorders, cardio-metabolic diseases, brain structure, sleep (approximated by 17 PGSs) and cognitive domains in The Maastricht Study (N = 2,499). We combined the significant PGSs in a multi-PGS model and used linear regression (with covariates for age, sex, genotyping batch, and ancestry) to estimate the incremental effect of the LIBRA score on single-PGS and multi-PGS models, comparing the partial R-squared values for PGSs and LIBRA across different models. We adjusted for Type 2 Diabetes (T2D) in our analyses and compared these results with non-adjusted models, thereby reinforcing the robustness of our findings across different populations. Intelligence (IQ) PGSs showed the strongest correlation with overall cognitive function (standardized β±SE=0.100±0.012, p < 0.001). 10 out of 17 PGSs maintained statistical significance in single-PGS models (FDR-corrected) and were selected in the multi-PGS model (additive adjusted R2=2.3%). The inclusion of LIBRA in both single-PGS and multi-PGS models increased the explained variance of overall cognition (additive R2=2.9% in the single-PGS model vs additive R2=2.3% in the multi-PGS model), but no significant gene-environment interactions were observed. Our study shows that incorporating information on genetic predispositions and environmental influences improves the explanation of cognition phenotypes. This comprehensive approach has shed some light on the factors influencing cognition. This information, along with further research, could contribute to the early identification of potential cognitive deficits and their risk factors. However, the relatively low amount of variance explained by these models suggests the need for continued exploration of other genetic, environmental, and lifestyle factors that might significantly impact cognitive health." @default.
• W4387496765 created "2023-10-11" @default.
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• W4387496765 date "2023-10-01" @default.
• W4387496765 modified "2023-10-12" @default.
• W4387496765 title "T15. THE ADDITIVE VALUE OF BRAIN LIFESTYLE IN THE EXPLANATORY ABILITY OF POLYGENIC RISK PROFILES ON COGNITIVE PERFORMANCE IN AGING INDIVIDUALS" @default.
• W4387496765 doi "https://doi.org/10.1016/j.euroneuro.2023.08.303" @default.
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