Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index. (10th March 2015)

• Record Type: Journal Article
• Authors: Minster, Ryan L.; Sanders, Jason L.; Singh, Jatinder; Kammerer, Candace M.; Barmada, M. Michael; Matteini, Amy M.; Zhang, Qunyuan; Wojczynski, Mary K.; Daw, E. Warwick; Brody, Jennifer A.; Arnold, Alice M.; Lunetta, Kathryn L.; Murabito, Joanne M.; Christensen, Kaare; Perls, Thomas T.; Province, Michael A.; Newman, Anne B.
• Is Part Of: Journals of gerontology. Volume 70:Number 8(2015:Aug.)
• Page Start: 1003
• Page End: 1008
• Publication Date: 2015-03-10
• Subjects: Genetics -- Epidemiology -- Successful aging -- Longevity; Geriatrics -- Periodicals; Gerontology -- Periodicals; 618.97
• DOI: 10.1093/gerona/glv006
• Languages: English
• ISSNs: 1079-5006

Abstract

Abstract : 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.