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Genetic trade-offs between complex diseases and longevity.

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^-5 ) for SCZ and T2D were negatively correlated with longevity. While for the less significant SNPs (1x10^-5 < 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.

SUBMITTER: Hu D

PROVIDER: S-EPMC9282840 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Genetic trade-offs between complex diseases and longevity.

Hu Dingxue D Li Yan Y Zhang Detao D Ding Jiahong J Song Zijun Z Min Junxia J Zeng Yi Y Nie Chao C

Aging cell 20220626 7

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 schizophre ...[more]

PMID: 35754110

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Project description:The knowledge of genetic trends and trade-offs between growth and reproductive traits might be useful to understand the evolution of these traits in livestock and natural populations of animals. We estimated the genetic trends and trade-offs between pre-weaning growth and calving intervals of Nellore animals from a commercial farm. Two-trait animal models were used to estimate covariance components and breeding values (EBV) for direct and maternal genetic effects of pre-weaning growth and direct genetic effects of calving intervals. Regression analyses were performed to examine the relationship between direct and maternal EBV of pre-weaning growth and direct EBV of calving intervals (dependent variables) and the coefficient of generation of each animal (independent variable). We also performed regression analyses to examine the relationship between direct EBV of calving intervals (dependent variables) and direct and maternal EBV of pre-weaning growth (independent variables). The genetic trends for direct and maternal genetic effect for pre-weaning growth were significant and presented genetic evolution in the studied Nellore herd. The genetic trends for the reproductive traits were also significant but indicated genetic changes in an unfavorable way. The genetic correlations between direct effects of pre-weaning growth and calving intervals traits and the genetic correlations between maternal effects of pre-weaning growth traits and direct effects of calving interval traits were not different from zero. The presence of trade-offs between the direct effects of growth and reproductive traits were confirmed through regression from direct EBV of calving intervals over EBV of pre-weaning growth traits. In addition, regression analyses showed that selection to increase pre-weaning growth also increased calving intervals. Our results showed that pre-weaning growth and calving intervals are increasing over generations and that trade-offs occurred between those traits in the studied Nellore herd.

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Genetic trade-offs between complex diseases and longevity.

Publications

Genetic trade-offs between complex diseases and longevity.

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