Scott M Williams, Ph.D. Professor of Molecular Physiology and Biophysics E-mail: smwilliams@chgr.mc.vanderbilt.edu Population Genetics, Genetics of Health Disparity, Cardiovascular Genetics, Genetics of Pregnancy Outcome

My research interests focus on human population genetics and the differential distribution of disease-causing genes among populations. It is well known that different human populations have different prevalence rates of specific genetic diseases. These differences may be traced to either random, historical events relating to ancient small populations or to specific selection pressures in past environments. Therefore, the study of many genetic diseases requires intensive study of well-defined populations and an understanding of population specific histories and/or genetic differentiation among populations. Diseases being studied include hypertension, arterial thrombosis, preterm birth, and asthma.

For the case of hypertension, the research focuses on a West African population from Ghana, which served as one of the major source populations for the African-American genome. We are using association/linkage disequilibrium analyses of several candidate genes, including the renin-angiotensin-aldosterone system (RAAS), to dissect the genetic basis of this disease. Although we are examining the role of single polymorphisms (especially single nucleotide polymorphisms or SNPs) in these genes for association with blood pressure differences, special attention is being paid to interactions among SNPs in the same and different loci and the role that such interactions play in blood pressure modulation. To date, we have shown that individually, several candidate SNPs are not associated with hypertension in the Ghanaian population, but that these same SNPs show strong evidence of gene-gene interactions in hypertensive, but not normotensive subjects. These data are consistent with there being a complex set of genetic interactions that predispose to disease. Our results also suggest that many of the negative results for single locus studies of hypertension may be due to the fact that interactions among multiple genes predispose individuals to high blood pressure rather than the isolated effects of single genes. This work is currently being extended to a larger sample size and siblings to better dissect the extent and nature of disease associated interactions. A similar project has also recently begun to examine the role of complex genetic and gene-environment interactions in the development of risk factors for arterial thrombosis.