Do diseases have anything to do with longevity? The answer is yes and no. According to a recent study led by BGI-Research and published by Aging Cell, relationships between longevity and genetic risks of complex diseases are not always as expected, with increased disease genetic risks not necessarily linked to higher mortality. 

Genetic trade-offs between complex diseases and longevity published by Aging Cell

The study constructed a tool for measuring the genetic risk for having certain disease, the polygenic risk scores (PRSs), for 225 complex diseases or traits, based on the genetic data of 2,178 centenarians across 22 provinces in China and 2,299 middle-aged individuals living in the same region. The higher the PRS, the higher the risk of having certain genetic diseases. 

The researchers looked at whether high disease genetic risks are associated with lower probabilities of living longer. The result showed most of the PRSs of clinically diagnosed diseases were negatively correlated with longevity, including Parkinson's disease, inflammatory bowel disease, stroke, coronary artery disease, and kidney disease.

However, the PRSs of some psychiatric disorders, such as schizophrenia, autism spectrum disorder, insulin-related traits, and atopic dermatitis, were positively correlated with longevity - these positive correlations were not expected. 

Both schizophrenia and type-2-diabetes were reported to increase mortality in many studies. So, the researchers further investigated these intriguing associations and possible underlying mechanisms by looking at the PRS within cell-type groups. The results showed that the immune component of schizophrenia genetic risk was positively linked to longevity, and the renal component of type-2-diabetes genetic risk was the most deleterious. 

A more detailed look at individual genes was also performed. FOXO3 was a famous longevity-related gene. One variation of FOXO3 had a higher frequency in people who lived for a long time, and also correlated with a higher risk of schizophrenia.

The study suggested that “risk” or “beneficial” of a common genetic variant is conditional regarding its role in human aging, health, and lifespan. It confirmed the genetic risks of most fatal diseases will decrease the chance of being long-lived, while also identifying several traits, whose genetic components may have benefits for longevity.

“Our study provided evidence for the genetic trade-off theory,” says Yan Li, Senior research scientist at-BGI Research, “We emphasized the positive effects of disease risk alleles on longevity, which could help explain the origin of the genetic components of diseases.”

The study also identified how different genes influence disease in distinct directions. Researchers from Peking University, Zhejiang University and University of Chinese Academy of Sciences also participated in this study.

Learn more about the study: https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13654