Ryan L Minster1, Jason L Sanders2, Jatinder Singh1, Candace M Kammerer1, M Michael Barmada1, Amy M Matteini3, Qunyuan Zhang4, Mary K Wojczynski4, E Warwick Daw4, Jennifer A Brody5, Alice M Arnold6, Kathryn L Lunetta7, Joanne M Murabito8, Kaare Christensen9, Thomas T Perls10, Michael A Province4, Anne B Newman11. 1. Department of Human Genetics and. 2. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. 3. Division of Geriatric Medicine and Gerontology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. 4. Division of Statistical Genomics, School of Medicine, Washington University in St. Louis, Missouri. 5. Cardiovascular Health Research Unit, Department of Medicine and. 6. Department of Biostatistics, University of Washington, Seattle. 7. Department of Biostatistics, Boston University School of Public Health, Massachusetts. 8. National Heart, Lung and Blood Institute Framingham Heart Study, Massachusetts. Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Massachusetts. 9. Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense. 10. Section of Geriatrics, Department of Medicine, Boston University, Boston School of Medicine and Boston Medical Center, Massachusetts. 11. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. newmana@edc.pitt.edu.
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.
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.
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