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

TitelImmunochip analysis identifies association of the RAD50/IL13 region with human longevity.
MedientypJournal Article
Jahr der Veröffentlichung2016
AutorenFlachsbart F, Ellinghaus D, Gentschew L, Heinsen F-A, Caliebe A, Christiansen L, Nygaard M, Christensen K, Blanché H, Deleuze J-F, Derbois C, Galan P, Büning C, Brand S, Peters A, Strauch K, Müller-Nurasyid M, Hoffmann P, Nöthen MM, Lieb W, Franke A, Schreiber S, Nebel A
JournalAging Cell
Volume15
Ausgabe3
Pagination585-8
Datum der Veröffentlichung2016 06
ISSN1474-9726
SchlüsselwörterChromosomes, Human, Pair 5, DNA Repair Enzymes, DNA-Binding Proteins, Genetic Loci, Genome-Wide Association Study, Humans, Interleukin-13, Longevity, Oligonucleotide Array Sequence Analysis
Zusammenfassung

<p>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.</p>

DOI10.1111/acel.12471
Alternate JournalAging Cell
PubMed ID27004735
PubMed Central IDPMC4854908
Grant ListP01 AG008761 / AG / NIA NIH HHS / United States