To identify genetic bases for prominent age-associated changes, including cardiovascular risk factors and determinants of personality traits, in a founder population. The results of the study will extend the studies of aging-associated conditions of outbred populations.
Recent reports form the Baltimore Longitudinal Study on Aging (BLSA) and other population studies have identified some epidemiological and genetic risk factors for aging-associated diseases; but the majority of studies have been observational, determining the range of values for a phenotype as a function of aging. Further examination of the genetics of aging-associated conditions such as cardiovascular and personality-related features is especially difficult because 1) they are 'late-onset' conditions, affecting older individuals; and 2) they are 'complex traits', with a number of genes individually tipping the balance toward a phenotype in one or another subgroup of an outbred population
As one way to help overcome these obstacles, attention has increasingly focused on the promise of 'founder populations' for the simplification of complex trait analysis. Such rare populations arise from a delimited group living in a defined region for many centuries with minimal admixture from outside populations. The Sardinian population is one of the few that is both numerous and accessible enough, and one of the most extreme in its relative homogeneity. It can thus be studied for a wide variety of both frequent and relatively rare traits. The targeted region for the present study, Ogliastra, has a particularly isolated population of 60,000, in an area enclosed by two mountain ranges and the sea.
The proposed study will test critically the notion that such a population can indeed help to analyze the complex vascular and personality traits proposed for the study.
Concerning the choice and progress of the Project:
Constant environment (in rural towns)
In a first survey, the project team recruited over 6,100 subjects from a catchment area including four towns in east-central Sardinia and assessed a first list of >200 traits. The baseline
survey has been followed by follow-up visits that collected longitudinal data on the same traits collected at baseline but added assessment of frailty-related traits, namely measures of bone density and geometry, muscle
strength, and gait speed, and additional cardiovascular measures (see below). In the course of SardiNIA3, along with the expansion of the cohort and the addition of more traits (see below), increases in testing efficiency and
additional cost-sharing funds from Sardinian sources permit the completion of both Fourth Visits for the entire cohort and Fifth Visits for half the cohort. Also in current actions, DNA sequencing has recovered essentially all
of the genetic variation in the cohort, and further arrangements for an Outcome Study have also been made (see Course of the Project).