2018
DOI: 10.1101/363036
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Abstract: 26We use a multi-stage genome-wide association of 1 million parental lifespans of genotyped 27 subjects and data on mortality risk factors to validate previously unreplicated findings near 28 CDKN2B-AS1, ATXN2/BRAP, FURIN/FES, ZW10, PSORS1C3, and 13q21.31, and identify 29 and replicate novel findings near GADD45G, KCNK3, LDLR, POM121C, ZC3HC1, and ABO. 30 We also validate previous findings near 5q33.3/EBF1 and FOXO3, whilst finding contradictory 31 evidence at other loci. Gene set and tissue-specific analys… Show more

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Cited by 6 publications
(5 citation statements)
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“…A pathway analysis of the top genes most influenced by Lp(a) levels revealed that the main pathway identified appeared to involve dysregulation of genes encoding cell aging, chondrocyte development, and inflammatory pathways. These findings support the notion that plasma Lp(a) levels may be a key determinant of healthy aging, as supported by studies showing a strong association between Lp(a) levels and parental lifespan, health span, and all-cause mortality [78][79][80][81]. Pathways linking Lp(a) with cell aging may involve cellular senescence and cell cycle inhibition via the PI3K/AKT/mTOR pathway.…”
Section: Discussionsupporting
confidence: 83%
“…A pathway analysis of the top genes most influenced by Lp(a) levels revealed that the main pathway identified appeared to involve dysregulation of genes encoding cell aging, chondrocyte development, and inflammatory pathways. These findings support the notion that plasma Lp(a) levels may be a key determinant of healthy aging, as supported by studies showing a strong association between Lp(a) levels and parental lifespan, health span, and all-cause mortality [78][79][80][81]. Pathways linking Lp(a) with cell aging may involve cellular senescence and cell cycle inhibition via the PI3K/AKT/mTOR pathway.…”
Section: Discussionsupporting
confidence: 83%
“…Although lifespan is not very heritable in the population at large 3 recent studies have been able to identify 30,31 and replicate 46 some lifespan associated alleles that lower the risk of age related diseases. Our results imply that to find loci that promote survival to the highest ages in the population, genetic studies should be based on long lived cases including at least parental mortality information but preferably also mortality information of siblings and other first and second degree family members.…”
Section: Discussionmentioning
confidence: 99%
“…ATXN2 (chr 20) is involved in regulating mRNA and is linked to decline in cognitive function in older adults [57], general cognitive function [51] and neurodegenerative disorders [58]. The ATXN2/BRAP locus has a strong association with parenteral lifespan [59]. Another mapped gene close to ATXN2 and BRAP is SH2B3, which encodes lymphocyte adaptor protein LNK, and plays a role in human aging though the mechanism involved is not fully understood [60].…”
Section: Gene Mappingmentioning
confidence: 99%