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Genetic trade-offs between complex diseases and longevity.

Dingxue Hu1,2, Yan Li2, Detao Zhang2

  • 1College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.

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|June 27, 2022
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Summary
This summary is machine-generated.

Human longevity is influenced by genetic disease risks. Centenarians showed lower risks for stroke but higher risks for schizophrenia and type 2 diabetes, suggesting complex genetic trade-offs.

Keywords:
complex diseasegeneticshuman longevitypolygenic risk scoretrade-offs

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Area of Science:

  • Genetics
  • Longevity Research
  • Complex Disease Epidemiology

Background:

  • Human longevity is influenced by numerous complex diseases and traits.
  • The interplay between genetic predispositions to diseases and exceptional longevity remains underexplored.

Purpose of the Study:

  • To investigate the association between polygenic risk scores (PRSs) for 225 complex diseases/traits and human longevity.
  • To identify specific genetic risk factors that positively or negatively impact longevity.

Main Methods:

  • Construction of PRSs for 225 complex diseases/traits.
  • Evaluation of PRS associations with longevity in a cohort of 2178 centenarians and 2299 middle-aged individuals.
  • Stratification of PRSs by cell-type and significance level of single nucleotide polymorphisms (SNPs).

Main Results:

  • Centenarians exhibited lower genetic risks for stroke and hypotension.
  • Conversely, higher genetic risks for schizophrenia (SCZ) and type 2 diabetes (T2D) were observed in centenarians.
  • The immune component of SCZ risk positively correlated with longevity, while the renal component of T2D risk was detrimental. Significant SNPs for SCZ/T2D were negatively correlated with longevity, whereas less significant SNPs showed positive correlations.

Conclusions:

  • Identified genetically informed positive and negative factors influencing human longevity.
  • Provided insights into the evolutionary accumulation of disease risk alleles.
  • Offered evidence supporting the theory of genetic trade-offs between complex diseases and longevity.