Genetic trade-offs between complex diseases and longevity.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 35754110.
- Also identified by DOI 10.1111/acel.13654 and PMC identifier 9282840.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-5</sup> ) for SCZ and T2D were negatively correlated with longevity. While for the less significant SNPs (1x10<sup>-5</sup> < 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.
Medical subject headings
- Diabetes Mellitus, Type 2
- Longevity