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  A meta-analysis of genome-wide association studies identifies multiple longevity genes

Deelen, J., Evans, D. S., Arking, D. E., Tesi, N., Nygaard, M., Liu, X., et al. (2019). A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nat Commun, 10(1), 3669. doi:10.1038/s41467-019-11558-2.

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Deelen, J.1, Author           
Evans, D. S., Author
Arking, D. E., Author
Tesi, N., Author
Nygaard, M., Author
Liu, X., Author
Wojczynski, M. K., Author
Biggs, M. L., Author
van der Spek, A., Author
Atzmon, G., Author
Ware, E. B., Author
Sarnowski, C., Author
Smith, A. V., Author
Seppala, I., Author
Cordell, H. J., Author
Dose, J., Author
Amin, N., Author
Arnold, A. M., Author
Ayers, K. L., Author
Barzilai, N., Author
Becker, E. J., AuthorBeekman, M., AuthorBlanche, H., AuthorChristensen, K., AuthorChristiansen, L., AuthorCollerton, J. C., AuthorCubaynes, S., AuthorCummings, S. R., AuthorDavies, K., AuthorDebrabant, B., AuthorDeleuze, J. F., AuthorDuncan, R., AuthorFaul, J. D., AuthorFranceschi, C., AuthorGalan, P., AuthorGudnason, V., AuthorHarris, T. B., AuthorHuisman, M., AuthorHurme, M. A., AuthorJagger, C., AuthorJansen, I., AuthorJylha, M., AuthorKahonen, M., AuthorKarasik, D., AuthorKardia, S. L. R., AuthorKingston, A., AuthorKirkwood, T. B. L., AuthorLauner, L. J., AuthorLehtimaki, T., AuthorLieb, W., AuthorLyytikainen, L. P., AuthorMartin-Ruiz, C., AuthorMin, J., AuthorNebel, A., AuthorNewman, A. B., AuthorNie, C., AuthorNohr, E. A., AuthorOrwoll, E. S., AuthorPerls, T. T., AuthorProvince, M. A., AuthorPsaty, B. M., AuthorRaitakari, O. T., AuthorReinders, M. J. T., AuthorRobine, J. M., AuthorRotter, J. I., AuthorSebastiani, P., AuthorSmith, J., AuthorSorensen, T. I. A., AuthorTaylor, K. D., AuthorUitterlinden, A. G., Authorvan der Flier, W., Authorvan der Lee, S. J., Authorvan Duijn, C. M., Authorvan Heemst, D., AuthorVaupel, J. W., AuthorWeir, D., AuthorYe, K., AuthorZeng, Y., AuthorZheng, W., AuthorHolstege, H., AuthorKiel, D. P., AuthorLunetta, K. L., AuthorSlagboom, P. E., Author           Murabito, J. M., Author more..
Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006              

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Free keywords: Apolipoprotein E2/*genetics Apolipoprotein E4/*genetics Genome-Wide Association Study Heat-Shock Proteins/*genetics Humans Longevity/*genetics
 Abstract: Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) epsilon4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE epsilon2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

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 Dates: 2019-08-142019-08-16
 Publication Status: Issued
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 Identifiers: Other: 31413261
DOI: 10.1038/s41467-019-11558-2
ISSN: 2041-1723 (Electronic)2041-1723 (Linking)
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Title: Nat Commun
Source Genre: Journal
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Pages: - Volume / Issue: 10 (1) Sequence Number: - Start / End Page: 3669 Identifier: -