By Maryna Mullerman ’20

Human viability is the survival of individuals after birth, and more research is needed to understand how associated genetic factors affect human survival and life expectancy. Dr. Hakhamanesh Mostafavi and researchers at Columbia University in New York developed a method to recognize genetic variants that influence human survival. The proposed method would provide information about human fitness in the environment and the cost of longer lifespan.  

The team analyzed participants from the Genetic Epidemiology Research on Adult Health and Aging (GERA) and UK Biobank. They focused on individuals of different ages and sexes while testing for allele frequency differences. The researchers hypothesized that an allele’s frequency should be the same for all individuals if the allele did not affect viability. The study divided the participants into specific age bins to understand sex-linked and age-linked factors. The researchers also investigated the trends of allele frequencies while considering parental age of death. They examined the nicotine receptor gene CHRNA3, located at a locus involving a significant change in allele frequency regarding a father’s age of death. The model was also adopted to determine changes in the frequency of multiple genetic variants. The trends of 42 polygenic traits were investigated in a Genome-wide Association Study (GWAS), whose polygenic score was calculated to investigate associations between polygenic traits of evolutionary importance.

With the GERA participants’ age distribution, the method was useful for identifying allele frequency trends in middle-aged individuals, as the study successfully determined trends of the two alleles e4 and e3 for the APOE gene. The e4 allele for the APOE gene increased the risk of cardiovascular diseases and Alzheimer’s disease, while the e3 allele seemed to have a protective effect. The GWAS showed that delayed puberty in both males and females, along with delayed age at first birth (AFB) in females, was associated with higher chances of survival. However, detained puberty and AFB affect biological fitness in the environment.

The researchers’ method provides a new approach to investigating genetic variables and their effects on human survival and life expectancy. This provides researchers with new tools to explore genetic longevity in humans.

References:

1. H. Mostafavi, et. al., Identifying genetic variants that affect viability in large cohorts. PLOS Biology 15, (2017). doi: e2002458.
2. Image retrieved from: https://static.pexels.com/photos/109919/pexels-photo-109919.jpeg