Immunochip analysis identifies association of the <em>RAD50/IL13</em> region with human longevity - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Aging Cell Année : 2016

Immunochip analysis identifies association of the RAD50/IL13 region with human longevity

Résumé

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 99.0years) and 6368 controls (mean age 57.2years) by targeting known immune-associated loci covered by the Immunochip. The analysis of 142136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip-wide significant signal (P-Immunochip=7.01x10(-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 P-Immunochip<5x10(-4) for replication in two samples from France (1257 LLI, mean age 102.4years; 1811 controls, mean age 49.1years) and Denmark (493 LLI, mean age 96.2years; 740 controls, mean age 63.1years). 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 PImmunochip+Repl=5.42x10(-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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hal-02640091 , version 1 (28-05-2020)

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Friederike Flachsbart, David Ellinghaus, Liljana Gentschew, Femke-Anouska Heinsen, Amke Caliebe, et al.. Immunochip analysis identifies association of the RAD50/IL13 region with human longevity. Aging Cell, 2016, 15 (3), pp.585-588. ⟨10.1111/acel.12471⟩. ⟨hal-02640091⟩
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