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

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The SardiNIA study population cohort comprises over 6,200 subjects, aged 19-102, 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, as well as findings of genetic factors determining height as well as significant genes involved in determining the levels of vitamin B6, vitamin B12, folate, homocysteine, and uric acid: the identification of cardiovascular risk factors that include phospholambin in cardiac repolarization, Col4A1 in arterial stiffness, loci for blood pressure, many affecting adiposity; and findings of personality facets affecting under- and over-weight (see bibliography for a complete list). Additional 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. For example, 24 hour blood pressure measurements are being made, diet is being analyzed, and morphological features of the head are being measured by optical scans. 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. In an initial report on multiple sclerosis, a gene was identified (CBLB) that regulates the level of the immune response both in patients in Sardinia and in other populations and in a mouse model for the disease.