Exome-Wide Association Study Identifies FN3KRP and PGP as New Candidate Longevity Genes
Autor: | Martina Müller-Nurasyid, Markus M. Nöthen, Friederike Flachsbart, Annette Peters, Kaare Christensen, Sophie Chantalat, Stefan Schreiber, David Ellinghaus, Pilar Galan, Per Hoffmann, Almut Nebel, Lene Christiansen, Amke Caliebe, Hélène Blanché, Andre Franke, Konstantin Strauch, Marianne Nygaard, Wolfgang Lieb, Janina Dose, Guillermo G. Torres, Jean-François Deleuze |
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Rok vydání: | 2021 |
Předmět: |
Male
THE JOURNAL OF GERONTOLOGY: Biological Sciences Aging media_common.quotation_subject Longevity Locus (genetics) AcademicSubjects/MED00280 Humans Medicine Exome Genes and Mitochondria Allele Gene Alleles media_common Aged 80 and over HumanExome BeadChip Genetics business.industry Rare variants Middle Aged Phenotype Phosphoric Monoester Hydrolases Association study Phosphotransferases (Alcohol Group Acceptor) Healthy aging Regulatory sequence Association Study Healthy Aging Humanexome Beadchip Long-lived Individuals Rare Variants Case-Control Studies AcademicSubjects/SCI00960 Long-lived individuals Female Geriatrics and Gerontology business Phosphoglycolate phosphatase Genome-Wide Association Study |
Zdroj: | Torres, G G, Nygaard, M, Caliebe, A, Blanché, H, Chantalat, S, Galan, P, Lieb, W, Christiansen, L, Deleuze, J-F, Christensen, K, Strauch, K, Müller-Nurasyid, M, Peters, A, Nöthen, M M, Hoffmann, P, Flachsbart, F, Schreiber, S, Ellinghaus, D, Franke, A, Dose, J & Nebel, A 2021, ' Exome-wide association study identifies FN3KRP and PGP as new candidate longevity genes ', The journals of gerontology. Series A, Biological sciences and medical sciences, vol. 76, no. 5, pp. 786-795 . https://doi.org/10.1093/gerona/glab023 The Journals of Gerontology Series A: Biological Sciences and Medical Sciences J. Gerontol. A Biol. Sci. Med. Sci. 76, 786–795 (2021) |
ISSN: | 1758-535X 1079-5006 |
Popis: | Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62 488 common and rare coding variants in 1248 German long-lived individuals, including 599 centenarians and 6941 younger controls (age < 60 years). In a single-variant analysis, we observed an exome-wide significant association between rs1046896 in the gene fructosamine-3-kinase-related-protein (FN3KRP) and longevity. Noteworthy, we found the longevity allele C of rs1046896 to be associated with an increased FN3KRP expression in whole blood; a database look-up confirmed this effect for various other human tissues. A gene-based analysis, in which potential cumulative effects of common and rare variants were considered, yielded the gene phosphoglycolate phosphatase (PGP) as another potential longevity gene, though no single variant in PGP reached the discovery p-value (1 × 10E−04). Furthermore, we validated the previously reported longevity locus cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1). Replication of our results in a French longevity cohort was only successful for rs1063192 in CDKN2B-AS1. In conclusion, we identified 2 new potential candidate longevity genes, FN3KRP and PGP which may influence the phenotype through their role in metabolic processes, that is, the reverse glycation of proteins (FN3KRP) and the control of glycerol-3-phosphate levels (PGP). |
Databáze: | OpenAIRE |
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