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archiveJanuary 15, 2019

One million parental lifespans analyzed to find genetic variants tied to longevity

A genome-wide association study examined one million parental lifespans to map genetic variants linked to human longevity. The researchers, working with the eQTLGen Consortium, validated several previously uncertain loci near CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31. They identified and replicated new variants near ABO, ZC3HC1, and IGF2R. The team also validated earlier findings near 5q33.3/EBF1 and FOXO3. Gene set and cell-specific analyses showed that expression in fetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Genetic risk for dementia, cardiovascular disease, and lung cancer explained the most variance in lifespan. Polygenic scores showed a mean lifespan difference of around five years across the deciles.

Polygenic scores from parental lifespan data can illuminate genetic pathways in common age-related diseases and distinguish survival chances.

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