Immunochip analysis identifies association of the RAD50/IL13 region with human longevity |
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| Authors: | Liljana Gentschew Femke‐Anouska Heinsen Amke Caliebe Lene Christiansen Marianne Nygaard Kaare Christensen Hélène Blanché Jean‐François Deleuze Céline Derbois Pilar Galan Carsten Büning Stephan Brand Anette Peters Konstantin Strauch Martina Müller‐Nurasyid Per Hoffmann Markus M Nöthen Wolfgang Lieb Andre Franke Stefan Schreiber Almut Nebel |
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| Affiliation: | 1. Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany;2. Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany;3. Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern, Denmark, Odense, Denmark;4. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark;5. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark;6. Fondation Jean Dausset‐Centre du Polymorphisme Humain (CEPH), Paris, France;7. Centre National de Génotypage CNG‐IG‐CEA, Evry, France;8. Université Sorbonne Paris Cité‐UREN, Unité de Recherche en Epidémiologie Nutritionnelle;9. U557 Inserm;10. U1125 Inra;11. Cnam;12. Université Paris 13, CRNH IdF, Bobigny, France;13. Department of Gastroenterology, Hepatology and Endocrinology, Charité, Campus Mitte, Berlin, Germany;14. Department of Medicine II – Grosshadern, Ludwig‐Maximilians‐University Munich, Munich, Germany;15. Institute of Epidemiology II, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;16. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany;17. German Center for Diabetes Research, Neuherberg, Germany;18. Institute of Genetic Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany;19. Institute of Medical Informatics, Biometry and Epidemiology, Chair 20. of 21. Genetic Epidemiology, Ludwig‐Maximilians‐University Munich, Munich, Germany;22. Department of Medicine I, Ludwig‐Maximilians‐University Munich, Munich, Germany;23. Institute of Human Genetics, University of Bonn, Bonn, Germany;24. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany;25. Division of Medical Genetics, University Hospital Basel and Department of Biomedicine, University of Basel, Basel, Switzerland;26. Institute of Epidemiology and Popgen Biobank, Kiel University, Kiel, Germany;27. Clinic for Internal Medicine I, University Hospital of Schleswig‐Holstein, Kiel, Germany |
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| 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 99.0 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 (PImmunochip = 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 PImmunochip < 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 PImmunochip+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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| Keywords: | 5q31 1 genetic association human longevity
IL13
Immunochip
RAD50
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