AI Article Synopsis
- - Researchers examined the link between genetics, complex diseases, and human longevity by analyzing polygenic risk scores (PRSs) for 225 diseases/traits in a sample of 2,178 centenarians and 2,299 middle-aged individuals.
- - Findings revealed that centenarians had lower genetic risks for stroke and low blood pressure (hypotension), but higher risks for schizophrenia and type 2 diabetes compared to younger individuals.
- - The study highlighted that certain genetic factors, like those related to the immune system, could positively impact longevity, while others, particularly associated with kidney issues in diabetes, had detrimental effects, supporting the notion of genetic trade-offs affecting lifespan.
Article Abstract
Longevity was influenced by many complex diseases and traits. However, the relationships between human longevity and genetic risks of complex diseases were not broadly studied. Here, we constructed polygenic risk scores (PRSs) for 225 complex diseases/traits and evaluated their relationships with human longevity in a cohort with 2178 centenarians and 2299 middle-aged individuals. Lower genetic risks of stroke and hypotension were observed in centenarians, while higher genetic risks of schizophrenia (SCZ) and type 2 diabetes (T2D) were detected in long-lived individuals. We further stratified PRSs into cell-type groups and significance-level groups. The results showed that the immune component of SCZ genetic risk was positively linked to longevity, and the renal component of T2D genetic risk was the most deleterious. Additionally, SNPs with very small p-values (p ≤ 1x10 ) for SCZ and T2D were negatively correlated with longevity. While for the less significant SNPs (1x10 < p ≤ 0.05), their effects on disease and longevity were positively correlated. Overall, we identified genetically informed positive and negative factors for human longevity, gained more insights on the accumulation of disease risk alleles during evolution, and provided evidence for the theory of genetic trade-offs between complex diseases and longevity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282840 | PMC |
| http://dx.doi.org/10.1111/acel.13654 | DOI Listing |
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