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

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eQTLGen Consortium , Timmers , P R H J , Kettunen , J , Perola , M & Ripatti , S 2019 , ' Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances ' , eLife , vol. 8 , 39856 . https://doi.org/10.7554/eLife.39856

Title: Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances
Author: eQTLGen Consortium; Timmers, Paul R. H. J.; Kettunen, J.; Perola, M.; Ripatti, S.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, National Institute for Health and Welfare (THL)
University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2019-01-15
Language: eng
Number of pages: 40
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/298734
Abstract: 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.
Subject: WIDE ASSOCIATION
HUMAN LONGEVITY
RISK
GWAS
GENE
HERITABILITY
METAANALYSIS
POPULATION
SELECTION
MODELS
3111 Biomedicine
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