PuSH - Publication Server of Helmholtz Zentrum München: Immunochip analysis identifies association of the <em>RAD50/IL13</em> region with human longevity.

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Flachsbart, F.* ; Ellinghaus, D.* ; Gentschew, L.* ; Heinsen, F.A.* ; Caliebe, A.* ; Christiansen, L.* ; Nygaard, M.* ; Christensen, K.* ; Blanche, H.* ; Deleuze, J.F.* ; Derbois, C.* ; Galan, P.* ; Büning, C.* ; Brand, S.* ; Peters, A. ; Strauch, K. ; Müller-Nurasyid, M. ; Hoffmann, P.* ; Nöthen, M.M.* ; Lieb, W.* ; Franke, A.* ; Schreiber, S.* ; Nebel, A.*

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

Aging Cell 15, 585-588 (2016)

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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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