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Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index.
Wednesday,2015-04-29 10:14 America/Los_Angeles — zdrager
| Title | Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Minster, RL, Sanders, JL, Singh, J, Kammerer, CM, M Barmada, M, Matteini, AM, Zhang, Q, Wojczynski, MK, E Daw, W, Brody, JA, Arnold, AM, Lunetta, KL, Murabito, JM, Christensen, K, Perls, TT, Province, MA, Newman, AB |
| Journal | J Gerontol A Biol Sci Med Sci |
| Volume | 70 |
| Issue | 8 |
| Pagination | 1003-8 |
| Date Published | 2015 Aug |
| ISSN | 1758-535X |
| Keywords | Aging, Apolipoproteins E, Forkhead Transcription Factors, Genetic Linkage, Genome-Wide Association Study, Humans, Longevity, Polymorphism, Single Nucleotide, Quantitative Trait Loci |
| Abstract | <p><b>BACKGROUND: </b>The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems.</p><p><b>METHODS: </b>We conducted a genome-wide association study and a genome-wide linkage analysis to map quantitative trait loci associated with the HAI and a modified HAI weighted for mortality risk in 3,140 individuals selected for familial longevity from the Long Life Family Study. The genome-wide association study used the Long Life Family Study as the discovery cohort and individuals from the Cardiovascular Health Study and the Framingham Heart Study as replication cohorts.</p><p><b>RESULTS: </b>There were no genome-wide significant findings from the genome-wide association study; however, several single-nucleotide polymorphisms near ZNF704 on chromosome 8q21.13 were suggestively associated with the HAI in the Long Life Family Study (p < 10(-) (6)) and nominally replicated in the Cardiovascular Health Study and Framingham Heart Study. Linkage results revealed significant evidence (log-odds score = 3.36) for a quantitative trait locus for mortality-optimized HAI in women on chromosome 9p24-p23. However, results of fine-mapping studies did not implicate any specific candidate genes within this region of interest.</p><p><b>CONCLUSIONS: </b>ZNF704 may be a potential candidate gene for studies of the genetic underpinnings of longevity.</p> |
| DOI | 10.1093/gerona/glv006 |
| Alternate Journal | J. Gerontol. A Biol. Sci. Med. Sci. |
| PubMed ID | 25758594 |
| PubMed Central ID | PMC4506316 |
| Grant List | AG023629 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268200960009C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01HC25195 / HC / NHLBI NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N02HL64278 / HL / NHLBI NIH HHS / United States P30AG024827 / AG / NIA NIH HHS / United States R01 AG029451 / AG / NIA NIH HHS / United States R01AG29451 / AG / NIA NIH HHS / United States U01 AG023744 / AG / NIA NIH HHS / United States U01 AG023746 / AG / NIA NIH HHS / United States U01 AG023749 / AG / NIA NIH HHS / United States U01 AG023755 / AG / NIA NIH HHS / United States U01AG023712 / AG / NIA NIH HHS / United States U01AG023744 / AG / NIA NIH HHS / United States U01AG023746 / AG / NIA NIH HHS / United States U01AG023749 / AG / NIA NIH HHS / United States U01AG023755 / AG / NIA NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States |