title: Association of Aging-Related Endophenotypes With Mortality in 2 Cohort Studies: the Long Life Family Study and the Health, Aging and Body Composition Study.
abstract: 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.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Singh
authors.forename: Nicole
authors.initials: N
authors.lastname: Schupf
authors.forename: Robert
authors.initials: R
authors.lastname: Boudreau
authors.forename: Amy M
authors.initials: AM
authors.lastname: Matteini
authors.forename: Tanushree
authors.initials: T
authors.lastname: Prasad
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: YongMei
authors.initials: Y
authors.lastname: Liu
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001823:Body Composition; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D058068:Endophenotypes; D005260:Female; D006304:Health Status; D006801:Humans; D008136:Longevity; D008168:Lung / Q000502:physiology; D008297:Male; D009026:Mortality; D009043:Motor Activity; D014481:United States / Q000453:epidemiology
keywords: aging; endophenotypes; longevity; mortality