With the goal of determining genetic and epidemiological factors in age-related traits, we are applying new statistical approaches to look for covariates and hidden correlations in large population data sets. A particular focus is the NIA-sponsored study of the founder Sardinian population, where inter-relatedness and stable environment of the population over many generations can simplify the analysis. The study has been scoring >200 dichotomized traits (smoking, etc.) and 98 quantitative traits (endophenotypes or quantitative risk-related genetic or environmental factors) that can be scored on a continuous scale. The use of quantitative traits permits the study of the entire range of allelic variation in a population. Traits of special interest include a range of cardiovascular risk factors, anthropometric measurements, blood test values, and facets of personality. ? In a current contract, a team of Sardinian scientists has recruited over 6,100 subjects from a selected group of four towns in east-central Sardinia, and has measured all traits for each subject. The sample cohort numbers over half of the population of the region aged 14-102; they are native-born, and at least 96 percent are known to have all grandparents born in the same province. The group include 4933 phenotyped sib pairs, 4266 phenotyped parent-child pairs, >4069 phenotyped cousin pairs, and more than 6459 phenotyped avuncular pairs. This sample is large enough and well enough phenotyped to show that even in this founder population, the variance for individual traits is comparable to that in outbred populations; and it is large enough and interrelated enough to infer highly significant estimates of genetic heritability for traits. In the first publications from the study,we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We found a significant genetic component for every trait. ? With this cohort, full-genome scans with batteries of up to 500,000 single-nucleotide markers were conducted, and have pointed to genes/variants that determine a significant portion of the genetic contribution to variance for each trait studied. Several publications, including ones on genes associated with obesity, on lipids, and on the level of blood components, have been completed. In addition, second visits are ongoing and third visits will be carried out for the study cohort to permit the assessment of longitudinal trends and outcomes, as well as the assessment of additional phenotypes related to bone density and frailty as a function of age. ? Targeted data analysis has also been initiated to compare possible correlations with other large population cohort studies, including the Baltimore Longitudinal Study of Aging and the InCHIANTI study supported by the NIA.
| Strait, James B; Uda, Manuela; Lakatta, Edward G et al. (2009) Using new tools to define the genetic underpinnings of risky traits associated with coronary artery disease: the SardiNIA study. Trends Cardiovasc Med 19:69-75 |
| Balaci, Lenuta; Spada, Maria Cristina; Olla, Nazario et al. (2007) IRAK-M is involved in the pathogenesis of early-onset persistent asthma. Am J Hum Genet 80:1103-14 |
| Costa Jr, Paul T; Terracciano, Antonio; Uda, Manuela et al. (2007) Personality traits in Sardinia: testing founder population effects on trait means and variances. Behav Genet 37:376-87 |
| Pilia, Giuseppe; Chen, Wei-Min; Scuteri, Angelo et al. (2006) Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet 2:e132 |
