Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances
Clark DW; eQTLGen Consortium; Wilson JF; Shen X; Fischer K; Ning Z; Joshi PK; Esko T; Kutalik Z; Feng X; Bretherick AD; Lall K; Timmers PRHJ; Mounier N
Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances
Clark DW; eQTLGen Consortium
Wilson JF
Shen X
Fischer K
Ning Z
Joshi PK
Esko T
Kutalik Z
Feng X
Bretherick AD
Lall K
Timmers PRHJ
Mounier N
ELIFE SCIENCES PUBLICATIONS LTD
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042824859
https://urn.fi/URN:NBN:fi-fe2021042824859
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]