Association of Aging-Related Endophenotypes With Mortality in 2 Cohort Studies: the Long Life Family Study and the Health, Aging and Body Composition Study.

Journal Article (Journal Article)

One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process.

Full Text

Duke Authors

Cited Authors

  • Singh, J; Schupf, N; Boudreau, R; Matteini, AM; Prasad, T; Newman, AB; Liu, Y; Christensen, K; Kammerer, CM

Published Date

  • December 1, 2015

Published In

Volume / Issue

  • 182 / 11

Start / End Page

  • 926 - 935

PubMed ID

  • 26582777

Pubmed Central ID

  • PMC4668756

Electronic International Standard Serial Number (EISSN)

  • 1476-6256

Digital Object Identifier (DOI)

  • 10.1093/aje/kwv143


  • eng

Conference Location

  • United States