title: Replication of Genome-Wide Association Study Findings of Longevity in White, African American, and Hispanic Women: The Women's Health Initiative.
abstract: BACKGROUND
  No study has evaluated whether genetic factors are associated with longevity in African Americans or Hispanics, and it is unclear whether genetic factors are associated with healthy aging.
  
  
  METHODS
  In this prospective study, we determined whether 14 genetic variants previously associated with longevity in genome-wide association studies were associated with survival to ages 85 and 90 in 11,053 postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. The associations of these variants with healthy aging, defined as survival to age 85 without chronic diseases or disability, were also determined.
  
  
  RESULTS
  Among white women, three single nucleotide polymorphisms (SNPs) (rs2075650 [TOMM40], rs4420638 [APOC1], and rs429358 [APOE]) were significantly associated with survival to 90 years after correction for multiple testing (p < .001); rs4420638 and rs429358 were also significantly associated with healthy aging (p = .02). In African American women, no SNP was associated with longevity. In Hispanic women, 7 SNPs in linkage disequilibrium with a novel SNP, rs2149954, recently identified as being associated with increased longevity in a European population, were significantly associated with decreased survival to age 85 for carriers of the T versus C allele (p = .04). The association with decreased longevity was explained by higher risk of coronary heart disease in carriers of the T allele. There were no associations between FOXO3A SNPs and longevity in the analyses. In a meta-analysis, rs2075650 and rs429358 were significantly associated with longevity.
  
  
  CONCLUSIONS
  Future studies are needed to identify novel loci associated with longevity in African American and Hispanic women to determine biologic pathways regulating life span in these groups.
authors.affiliation: Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine.
authors.forename: Aladdin H
authors.initials: AH
authors.lastname: Shadyab
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.affiliation: Department of Epidemiology, University of Washington, Seattle.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Reiner
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jain
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Chancellor
authors.initials: C
authors.lastname: Hohensee
authors.affiliation: Division of Epidemiology, Graduate School of Public Health, San Diego State University, California.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Macera
authors.affiliation: Division of Epidemiology, Graduate School of Public Health, San Diego State University, California.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Shaffer
authors.affiliation: Department of Psychology, San Diego State University, California.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Gallo
authors.affiliation: Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine.
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000369:Aged, 80 and over; D000483:Alleles; D053302:Apolipoprotein C-I / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D044465:White People / Q000235:genetics*
chemical_list: C505803:APOC1 protein, human; D053302:Apolipoprotein C-I; D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
keywords: Aging; Gene; Minority; Successful aging