TY - JOUR T1 - Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index. JF - J Gerontol A Biol Sci Med Sci Y1 - 2015 A1 - Minster, Ryan L A1 - Sanders, Jason L A1 - Singh, Jatinder A1 - Kammerer, Candace M A1 - Barmada, M Michael A1 - Matteini, Amy M A1 - Zhang, Qunyuan A1 - Wojczynski, Mary K A1 - Daw, E Warwick A1 - Brody, Jennifer A A1 - Arnold, Alice M A1 - Lunetta, Kathryn L A1 - Murabito, Joanne M A1 - Christensen, Kaare A1 - Perls, Thomas T A1 - Province, Michael A A1 - Newman, Anne B KW - Aging KW - Apolipoproteins E KW - Forkhead Transcription Factors KW - Genetic Linkage KW - Genome-Wide Association Study KW - Humans KW - Longevity KW - Polymorphism, Single Nucleotide KW - Quantitative Trait Loci AB -

BACKGROUND: The Healthy Aging Index (HAI) is a tool for measuring the extent of health and disease across multiple systems.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: ZNF704 may be a potential candidate gene for studies of the genetic underpinnings of longevity.

VL - 70 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25758594?dopt=Abstract ER -