Aging-related Traits and Disease Risk Factors in a Sardinian Population Cohort

$402,202ZIAFY2009AGNIH

National Institute On Aging

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Abstract

The SardiNIA study population cohort comprises over 6,100 subjects, aged 14-102, from a cluster of four towns in Sardinia. The study has been measuring >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. Traits of special interest include a range of cardiovascular risk factors, anthropometric measurements, blood test values, and facets of personality. With this cohort, full-genome scans with batteries of up to 1,000,000 single-nucleotide markers were conducted, and genome-wide association scans (GWAS) have pointed to genes/variants that determine a significant portion of the genetic contribution to variance for each trait studied. In conjunction with consortium efforts on other population cohorts, including the Baltimore Longitudinal Study of Aging and the InCHIANTI study supported by the NIA, an increasing number of publications have resulted that identify genes associated with obesity, cardiovascular traits, and levels of lipids and blood components. In particular, genes associated with uric acid as a cardiovascular risk factor and with HbF levels as a modulator of thalassemia/sickle cell disease severity have been identified. In the past year, a number of studies have been completed on levels of blood components and of lipids and anthropometric measures. They included the finding of genes involved in the determination of levels of vitamin B6, vitamin B12, folate, homocysteine, and uric acid (for which 5 new genes were found); the identification of cardiovascular risk factors that include phospholambin in cardiac repolarization, Col4A1 in arterial stiffness, 8 loci for blood pressure, and 3 affecting adiposity;and findings of personality facets affecting under- and over-weight. In addition, third visits are in process 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. In a complementary approach, the genetic studies are being extended to clinical series of Sardinian patients and controls for several diseases, including breast cancer and autoimmune diseases, all of which have a very high incidence on the island.

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