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

Flachsbart, Friederike; Ellinghaus, David; Gentschew, Liljana; Heinsen, Femke-Anouska; Caliebe, Amke; Christiansen, Lene; Nygaard, Marianne; Christensen, Kaare; Blanche, Helene; Deleuze, Jean-Francois; Derbois, Celine; Galan, Pilar; Büning, Carsten; Brand, Stephan; Peters, Annette ; Strauch, Konstantin; Müller-Nurasyid, Martina; Hoffmann, Per; Nöthen, Markus M.; Lieb, Wolfgang; Franke, Andre; Schreiber, Stefan und Nebel, Almut (2016): Immunochip analysis identifies association of the RAD50/IL13 region with human longevity. In: Aging Cell, Bd. 15, Nr. 3: S. 585-588

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1474-9718
• Sprache: Englisch