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Immunochip analysis identifies association of the RAD50/IL13 region with human longevity.
Aging Cell 15, 585-588 (2016)
Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on chromosome 5q31.1 using a combined European sample of 3208 long-lived individuals (LLI) and 8919 younger controls. First, we performed a large-scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (PI mmunochip = 7.01 × 10(-9) ) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PI mmunochip < 5 × 10(-4) for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta-analysis of the combined French and Danish data after adjusting for multiple testing. In a meta-analysis of all three samples, rs2706372 reached a P-value of PI mmunochip+Repl = 5.42 × 10(-7) (OR = 1.20; 95% CI = 1.12-1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Il13 ; Rad50 ; 5q31.1 ; Immunochip ; Genetic Association ; Human Longevity; Genome-wide Association; Survival; Disease; Locus; Apoe; Metaanalysis; Complex; Gene; Age
ISSN (print) / ISBN
1474-9718
e-ISSN
1474-9726
Zeitschrift
Aging Cell
Quellenangaben
Band: 15,
Heft: 3,
Seiten: 585-588
Verlag
Wiley
Verlagsort
Hoboken
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed