Heritability estimates of endophenotypes of long and health life: the Long Life Family Study.
BACKGROUND
Identification of gene variants that contribute to exceptional survival may provide critical biologic information that informs optimal health across the life span.


METHODS
As part of phenotype development efforts for the Long Life Family Study, endophenotypes that represent exceptional survival were identified and heritability estimates were calculated. Principal components (PCs) analysis was carried out using 28 physiologic measurements from five trait domains (cardiovascular, cognition, physical function, pulmonary, and metabolic).


RESULTS
The five most dominant PCs accounted for 50% of underlying trait variance. The first PC (PC1), which consisted primarily of poor pulmonary and physical function, represented 14.3% of the total variance and had an estimated heritability of 39%. PC2 consisted of measures of good metabolic and cardiovascular function with an estimated heritability of 27%. PC3 was made up of cognitive measures (h(2) = 36%). PC4 and PC5 contained measures of blood pressure and cholesterol, respectively (h(2) = 25% and 16%).


CONCLUSIONS
These PCs analysis-derived endophenotypes may be used in genetic association studies to help identify underlying genetic mechanisms that drive exceptional survival in this and other populations.
Matteini
Amy M
AM
Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. amatteini@jhmi.edu
Fallin
M Daniele
MD
Kammerer
Candace M
CM
Schupf
Nicole
N
Yashin
Anatoli I
AI
Christensen
Kaare
K
Arbeev
Konstantin G
KG
Barr
Graham
G
Mayeux
Richard
R
Newman
Anne B
AB
Walston
Jeremy D
JD
D002320:Cardiovascular Physiological Phenomena; D008076:Cholesterol, HDL / Q000097:blood; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D058068:Endophenotypes; D005541:Forced Expiratory Volume / Q000235:genetics; D014644:Genetic Variation / Q000502:physiology*; D018737:Hand Strength / Q000502:physiology; D006304:Health Status; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008168:Lung / Q000502:physiology; D008660:Metabolism / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D054561:National Institute on Aging (U.S.); D025341:Principal Component Analysis; D019655:Quantitative Trait, Heritable; D014481:United States; D055105:Waist Circumference / Q000235:genetics
D008076:Cholesterol, HDL
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