Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances



: Timmers PRHJ, Mounier N, Lall K, Fischer K, Ning Z, Feng X, Bretherick AD, Clark DW; eQTLGen Consortium, Shen X, Esko T, Kutalik Z, Wilson JF, Joshi PK

Publisher: ELIFE SCIENCES PUBLICATIONS LTD

: 2019

eLife

ELIFE

: ELIFE

: ARTN e39856

: 8

: 1

: 40

: 40

: 2050-084X

DOI: https://doi.org/10.7554/eLife.39856

: https://research.utu.fi/converis/portal/detail/Publication/39183399


We use a 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 ABO, ZC3HC1, and IGF2R. We also validate previous findings near 5q33.3/EBF1 and FOXO3, whilst finding contradictory evidence at other loci. Gene set and cell-specific analyses show that expression in foetal 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. Resulting polygenic scores show a mean lifespan difference of around five years of life across the deciles.

Last updated on 2024-26-11 at 21:45