Wright · G3 (Bethesda, Md.) 2019 · Genome-wide association study and meta-analysis · n=>650,000

A Prospective Analysis of Genetic Variants Associated with Human Lifespan.

Level 3 - non-randomized controlled study

Meta-analysis of observational genome-wide association cohorts

PubMed 31484785 · doi:10.1534/g3.119.400448 · record verified 2026-08-26

What was done

Researchers conducted a genome-wide association study (GWAS) on parental lifespan using a de-identified AncestryDNA cohort of over 300,000 genotyped individuals linked to pedigrees containing over 400,000,000 people. They compared these findings against a GWAS using subject age as a proxy trait. The AncestryDNA data were then combined with the UK Biobank dataset in a meta-analysis totaling more than 650,000 individuals to identify loci associated with parental lifespan and estimate the variance explained by genome-wide polymorphisms.

What was found

The initial AncestryDNA GWAS identified 6 genome-wide significant loci linked to parental lifespan. Comparing age and lifespan GWAS results revealed that only one locus, APOE, was associated with both traits. The combined meta-analysis of over 650,000 individuals identified 15 parental lifespan-associated loci. Genome-wide polymorphisms accounted for up to 8% of the variance in human lifespan.

Why it matters

The study identifies specific genomic loci tied to longevity and demonstrates that common genetic variants account for a notable share (up to 8%) of human lifespan variance, while showing that age alone is a limited proxy for lifespan genetics outside of APOE.

Limits

The study evaluated parental lifespan rather than direct subject lifespan. Specific effect sizes, confidence intervals, individual locus identities beyond APOE, and demographic or ancestral distributions are not detailed in the abstract.

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