“Genomic Underpinnings of Lifespan Allow Prediction and Reveal Basis in Modern Risks”, 2018-07-06 (; backlinks; similar):
We use a multi-stage genome-wide association of 1 million parental lifespans of genotyped subjects and data on mortality risk factors to validate previously unreplicated findings near CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31, and identify and replicate novel findings near GADD45G, KCNK3, LDLR, POM121C, ZC3HC1, and ABO.
Gene set and tissue-specific analyses show that expression in fetal brain cells and adult dorsolateral prefrontal cortex is enriched for lifespan variation, as are gene pathways involving lipid proteins and homeostasis, vesicle-mediated transport, and synaptic function. Individual genetic variants that increase dementia, cardiovascular disease, and lung cancer—but not other cancers—explain the most variance, possibly reflecting modern susceptibilities, whilst cancer may act through many rare variants, or the environment.
Resultant polygenic scores predict a mean lifespan difference of around 5 years of life across the deciles.