title: Genome-Wide Association Study and Linkage Analysis of the Healthy Aging Index.
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.
authors.affiliation: Department of Human Genetics and.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Minster
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Sanders
authors.affiliation: Department of Human Genetics and.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Singh
authors.affiliation: Department of Human Genetics and.
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.affiliation: Department of Human Genetics and.
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.affiliation: Division of Geriatric Medicine and Gerontology, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Matteini
authors.affiliation: Division of Statistical Genomics, School of Medicine, Washington University in St. Louis, Missouri.
authors.forename: Qunyuan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Division of Statistical Genomics, School of Medicine, Washington University in St. Louis, Missouri.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wojczynski
authors.affiliation: Division of Statistical Genomics, School of Medicine, Washington University in St. Louis, Missouri.
authors.forename: E Warwick
authors.initials: EW
authors.lastname: Daw
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine and.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Brody
authors.affiliation: Department of Biostatistics, University of Washington, Seattle.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Arnold
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Massachusetts.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.affiliation: National Heart, Lung and Blood Institute Framingham Heart Study, Massachusetts. Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Massachusetts.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
authors.affiliation: Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Section of Geriatrics, Department of Medicine, Boston University, Boston School of Medicine and Boston Medical Center, Massachusetts.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Perls
authors.affiliation: Division of Statistical Genomics, School of Medicine, Washington University in St. Louis, Missouri.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Province
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania. newmana@edc.pitt.edu.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
mesh_terms: D000375:Aging; D001057:Apolipoproteins E / Q000235:genetics; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D001057:Apolipoproteins E; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors
keywords: Epidemiology; Genetics; Longevity; Successful aging