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Genes that appear influence longevity in humans have been uncovered by researchers from Columbia University, offering us new insights into the evolutionary fitness of humans. The work was presented as a proof-of-concept study at the Biology of Genomes meeting at Cold Spring Harbour this week.

The team theorised that a gene which affected longevity in humans would be found at different frequencies across multiple age brackets, whereas one that did not would remain constant. To explore this hypothesis, they assembled multiple large cohorts that accounted for different ancestries and examined their genomic data.

One such cohort was made up of roughly 58,000 participants of European descent from the Resource for Genetic Epidemiology Research on Aging (GERA). The team found that the strongest signal was from the ε4 allele of the APOE gene, which is known to be linked to increased risk of late-onset Alzheimer’s. The frequency of the variant dropped significantly in participants over 70 years old, the age at which Alzheimer’s often manifests.

Another cohort of 96,000 participants with European ancestry was assembled from donors to the UK Biobank. These participants had provided information about the deaths of their parents and so the team used the participants as a proxy for the older generation to establish which genes had influenced their death.

Using this data, they identified a signal near the CHRNA3 gene which was linked to the paternal age of death. Variants located near CHRNA3 have previously been associated with smoking, with people carrying the variant smoking more than those without.

The team also used genome wide associated studies to generate polygenic risk scores for roughly 40 genes to account for conditions that were reliant on multiple loci. With the UK Biobank cohort, these scores allowed the team to observe that variants linked to cholesterol, BMI, and coronary artery disease risk were all negatively associated with longevity in fathers. On both the maternal and paternal side, variants linked to later puberty timing increased longevity, as did a higher age for birth of their first child in mothers.

While this research supports the initial hypothesis put forwards by the team, it also demonstrates the complexity of how our genomes can govern our lifespans. Nonetheless, it offers us significant insight into the subtle impact genetic variants can have on our lives.

Hakhamanesh Mostafavi, one of the researchers in the study, said, “We have a much more comprehensive picture of viability in humans.”

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