Genome Wide Association Study and Linkage Analysis of the Healthy Aging Index.
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.
The journals of gerontology. Series A, Biological sciences and medical sciences