Vanderbilt University School of Medicine

Williams, Scott M. , Ph.D.

Lab Url: N/A

Phone Number: (615) 322-8036


Williams, Scott's picture

Office Address   Mailing Address

519 Light Hall

519 Light Hall 0700

Research Keywords
Population genetics, complex disease,Genetics,Human Genetics,Vascular Biology

Research Specialty
Genetics of hypertension and keloids; Genetic structure of African populations

Research Description
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. In my laboratory, the focus of this approach is on one class of diseases that are more common in people of sub-Saharan African descent. Specifically, we are using the genetics of fibroproliferative diseases in Africans and African-Americans as a model for understanding the differential distribution of genetic disease.

One such disease is hypertension. The research on this disease 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.

Edwards, DR, Romero, R, Kusanovic, JP, Hassan, SS, Mazaki-Tovi, S, Vaisbuch, E, Kim, CJ, Erez, O, Chaiworapongsa, T, Pearce, BD, Bartlett, J, Friel, LA, Salisbury, BA, Anant, MK, Vovis, GF, Lee, MS, Gomez, R, Behnke, E, Oyarzun, E, Tromp, G, Menon, R, Williams, SM. Polymorphisms in maternal and fetal genes encoding for proteins involved in extracellular matrix metabolism alter the risk for small-for-gestational-age. J Matern Fetal Neonatal Med, 24(2), 362-80, 2011. PMCID:2923624

Epplein, M, Signorello, LB, Zheng, W, Peek, RM, Michel, A, Williams, SM, Pawlita, M, Correa, P, Cai, Q, Blot, WJ. Race, African ancestry, and Helicobacter pylori infection in a low-income United States population. Cancer Epidemiol Biomarkers Prev, , , 2011.

Lemons, CJ, Key, AP, Fuchs, D, Yoder, PJ, Fuchs, LS, Compton, DL, Williams, SM, Bouton, B. Predicting Reading Growth with Event-Related Potentials: Thinking Differently about Indexing "Responsiveness&quot. Learn Individ Differ, 20(3), 158-166, 2010. PMCID:2939920

Muszkat, M, Kurnik, D, Sofowora, GG, Solus, J, Xie, HG, Harris, PA, Williams, SM, Wood, AJ, Stein, CM. Desensitization of vascular response in vivo: contribution of genetic variation in the [alpha]2B-adrenergic receptor subtype. J Hypertens, 28(2), 278-84, 2010. PMCID:2895551

Russell, SB, Russell, JD, Trupin, KM, Gayden, AE, Opalenik, SR, Nanney, LB, Broquist, AH, Raju, L, Williams, SM. Epigenetically altered wound healing in keloid fibroblasts. J Invest Dermatol, 130(10), 2489-96, 2010. PMCID:2939920

Ryckman, KK, Fielding, K, Hill, AV, Mendy, M, Rayco-Solon, P, Sirugo, G, van der Sande, MA, Waight, P, Whittle, HC, Hall, AJ, Williams, SM, Hennig, BJ. Host genetic factors and vaccine-induced immunity to HBV infection: haplotype analysis. PLoS One, 5(8), e12273, 2010. PMCID:2923624

Ryckman, KK, Morken, NH, White, MJ, Velez, DR, Menon, R, Fortunato, SJ, Magnus, P, Williams, SM, Jacobsson, B. Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth. PLoS One, 5(2), e9040, 2010. PMCID:2815792

Williams, SM. Endophenotypes, heritability, and underlying complexity in hypertension. Am J Hypertens, 23(8), 819, 2010. PMCID:2923624

Williams, SM, Velez, DR, Menon, R. Geographic ancestry and markers of preterm birth. Expert Rev Mol Diagn, 10(1), 27-32, 2010. PMCID:2895551

Moore, PE, Ryckman, KK, Williams, SM, Patel, N, Summar, ML, Sheller, JR. Genetic variants of GSNOR and ADRB2 influence response to albuterol in African-American children with severe asthma. Pediatr Pulmonol, 44(7), 649-54, 2009.

Ryckman, KK, Simhan, HN, Krohn, MA, Williams, SM. Cervical cytokine network patterns during pregnancy: the role of bacterial vaginosis and geographic ancestry. J Reprod Immunol, 79(2), 174-82, 2009.

Ryckman, KK, Simhan, HN, Krohn, MA, Williams, SM. Predicting risk of bacterial vaginosis: the role of race, smoking and corticotropin-releasing hormone-related genes. Mol Hum Reprod, 15(2), 131-7, 2009.

Ryckman, KK, Williams, SM, Krohn, MA, Simhan, HN. Genetic association of Toll-like receptor 4 with cervical cytokine concentrations during pregnancy. Genes Immun, 10(7), 636-40, 2009.

Sile, S, Velez, DR, Gillani, NB, Narsia, T, Moore, JH, George, AL, Vanoye, CG, Williams, SM. CLCNKB-T481S and essential hypertension in a Ghanaian population. J Hypertens, 27(2), 298-304, 2009.

Ciarleglio, CM, Ryckman, KK, Servick, SV, Hida, A, Robbins, S, Wells, N, Hicks, J, Larson, SA, Wiedermann, JP, Carver, K, Hamilton, N, Kidd, KK, Kidd, JR, Smith, JR, Friedlaender, J, McMahon, DG, Williams, SM, Summar, ML, Johnson, CH. Genetic differences in human circadian clock genes among worldwide populations. J Biol Rhythms, 23(4), 330-40, 2008. PMCID:2579796

Fortunato, SJ, Menon, R, Velez, DR, Thorsen, P, Williams, SM. Racial disparity in maternal-fetal genetic epistasis in spontaneous preterm birth. Am J Obstet Gynecol, 198(6), 666.e1-9; discussion 666.e9-10, 2008.

Kurnik, D, Li, C, Sofowora, GG, Friedman, EA, Muszkat, M, Xie, HG, Harris, PA, Williams, SM, Nair, UB, Wood, AJ, Stein, CM. Beta-1-adrenoceptor genetic variants and ethnicity independently affect response to beta-blockade. Pharmacogenet Genomics, 18(10), 895-902, 2008. PMCID:2757009

Moore, PE, Williams, SM, Gebretsadik, T, Jiang, L, Minton, PL, Shintani, A, Phillips Iii, JA, Dawson, EP, Hartert, TV. beta(2)-adrenergic receptor promoter haplotype influences spirometric response during an acute asthma exacerbation. Clin Transl Sci, 1(2), 155-61, 2008. PMCID:2757009

Ryckman, K, Williams, SM. Calculation and use of the Hardy-Weinberg model in association studies. Curr Protoc Hum Genet, Chapter 1, Unit 1.18, 2008.

Ryckman, KK, Jiang, L, Li, C, Bartlett, J, Haines, JL, Williams, SM. A prevalence-based association test for case-control studies. Genet Epidemiol, , , 2008.

Ryckman, KK, Williams, SM, Kalinka, J. Correlations of selected vaginal cytokine levels with pregnancy-related traits in women with bacterial vaginosis and mycoplasmas. J Reprod Immunol, , , 2008.

Ryckman, KK, Williams, SM, Krohn, MA, Simhan, HN. Racial differences in cervical cytokine concentrations between pregnant women with and without bacterial vaginosis. J Reprod Immunol, , , 2008. PMCID:2518392

Schoenhard, JA, Asselbergs, FW, Poku, KA, Stocki, SA, Gordon, S, Vaughan, DE, Brown, NJ, Moore, JH, Williams, SM. Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. Hum Genet, 124(5), 479-88, 2008.

Sile, S, Velez, DR, Gillani, NB, Alexander, CA, Alexander, CR, George, AL, Williams, SM. Haplotype diversity in four genes (CLCNKA, CLCNKB, BSND, NEDD4L) involved in renal salt reabsorption. Hum Hered, 65(1), 33-46, 2008.

Velez, DR, Fortunato, SJ, Morgan, N, Edwards, TL, Lombardi, SJ, Williams, SM, Menon, R. Patterns of cytokine profiles differ with pregnancy outcome and ethnicity. Hum Reprod, , , 2008.

Velez, DR, Fortunato, SJ, Thorsen, P, Lombardi, SJ, Williams, SM, Menon, R. Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants. PLoS One, 3(9), e3283, 2008. PMCID:2553267

Velez, DR, Fortunato, SJ, Williams, SM, Menon, R. Interleukin-6 (IL-6) and receptor (IL6-R) gene haplotypes associate with amniotic fluid protein concentrations in preterm birth. Hum Mol Genet, 17(11), 1619-30, 2008.

Velez, DR, Menon, R, Simhan, H, Fortunato, S, Canter, JA, Williams, SM. Mitochondrial DNA variant A4917G, smoking and spontaneous preterm birth. Mitochondrion, 8(2), 130-5, 2008.

Asselbergs, FW, Williams, SM, Hebert, PR, Coffey, CS, Hillege, HL, Navis, G, Vaughan, DE, van Gilst, WH, Moore, JH. Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels. Genomics, 89(3), 362-9, 2007. PMCID:1808222

Cauci, S, Di Santolo, M, Casabellata, G, Ryckman, K, Williams, SM, Guaschino, S. Association of interleukin-1{beta} and interleukin-1 receptor antagonist polymorphisms with bacterial vaginosis in non-pregnant Italian women. Mol Hum Reprod, , , 2007.

Pennell, CE, Jacobsson, B, Williams, SM, Buus, RM, Muglia, LJ, Dolan, SM, Morken, NH, Ozcelik, H, Lye, SJ, , , Relton, C. Genetic epidemiologic studies of preterm birth: guidelines for research. Am J Obstet Gynecol, 196(2), 107-118, 2007.

Schneider, BG, Camargo, MC, Ryckman, KK, Sicinschi, LA, Piazuelo, MB, Zabaleta, J, Correa, P, Williams, SM. Cytokine polymorphisms and gastric cancer risk: An evolving view. Cancer Biol Ther, 7(2), , 2007.

Sile, S, Gillani, NB, Velez, DR, Vanoye, CG, Yu, C, Byrne, LM, Gainer, JV, Brown, NJ, Williams, SM, George, AL. Functional BSND variants in essential hypertension. Am J Hypertens, 20(11), 1176-1182, 2007.

Velez, DR, Menon, R, Thorsen, P, Jiang, L, Simhan, H, Morgan, N, Fortunato, SJ, Williams, SM. Ethnic differences in interleukin 6 (IL-6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels. Ann Hum Genet, 71(Pt 5), 586-600, 2007.

Velez, DR, White, BC, Motsinger, AA, Bush, WS, Ritchie, MD, Williams, SM, Moore, JH. A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction. Genet Epidemiol, , , 2007.

Williams, SM, Stocki, S, Jiang, L, Brew, K, Gordon, S, Vaughan, DE, Brown, NJ, Poku, KA, Moore, JH. A population-based study in Ghana to investigate inter-individual variation in plasma t-PA and PAI-1. Ethn Dis, 17(3), 492-7, 2007.

Agirbasli, D, Agirbasli, M, Williams, SM, Phillips, JA. Interaction among 5,10 methylenetetrahydrofolate reductase, plasminogen activator inhibitor and endothelial nitric oxide synthase gene polymorphisms predicts the severity of coronary artery disease in Turkish patients. Coron Artery Dis, 17(5), 413-7, 2006.

Dudek, SM, Motsinger, AA, Velez, DR, Williams, SM, Ritchie, MD. Data simulation software for whole-genome association and other studies in human genetics. Pac Symp Biocomput, , 499-510, 2006.

Johnson, RL, Williams, SM, Spruill, IJ. Genomics, nutrition, obesity, and diabetes. J Nurs Scholarsh, 38(1), 11-8, 2006.

Kurnik, D, Muszkat, M, Li, C, Sofowora, GG, Solus, J, Xie, HG, Harris, PA, Jiang, L, McMunn, C, Ihrie, P, Dawson, EP, Williams, SM, Wood, AJ, Stein, CM. Variations in the alpha(2A)-adrenergic receptor gene and their functional effects. Clin Pharmacol Ther, 79(3), 173-85, 2006.

Lohmueller, KE, Wong, LJ, Mauney, MM, Jiang, L, Felder, RA, Jose, PA, Williams, SM. Patterns of Genetic Variation in the Hypertension Candidate Gene GRK4: Ethnic Variation and Haplotype Structure. Ann Hum Genet, 70(Pt 1), 27-41, 2006.

Menon, R, Fortunato, SJ, Thorsen, P, Williams, S. Genetic associations in preterm birth: a primer of marker selection, study design, and data analysis. J Soc Gynecol Investig, 13(8), 531-41, 2006.

Menon, R, Merialdi, M, Betr?!n, AP, Dolan, S, Jiang, L, Fortunato, SJ, Williams, S. Analysis of association between maternal tumor necrosis factor-alpha promoter polymorphism (-308), tumor necrosis factor concentration, and preterm birth. Am J Obstet Gynecol, 195(5), 1240-8, 2006.

Menon, R, Velez, DR, Simhan, H, Ryckman, K, Jiang, L, Thorsen, P, Vogel, I, Jacobsson, B, Merialdi, M, Williams, SM, Fortunato, SJ. Multilocus interactions at maternal tumor necrosis factor-alpha, tumor necrosis factor receptors, interleukin-6 and interleukin-6 receptor genes predict spontaneous preterm labor in European-American women. Am J Obstet Gynecol, 194(6), 1616-24, 2006.

Menon, R, Velez, DR, Thorsen, P, Vogel, I, Jacobsson, B, Williams, SM, Fortunato, SJ. Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors. Hum Hered, 62(2), 107-18, 2006.

Pennell, CE, Jacobsson, B, Williams, SM, Buus, RM, Muglia, LJ, Dolan, SM, Morken, NH, Ozcelik, H, Lye, SJ, Prebic Genetics Working Group, , Relton, C. Genetic epidemiological studies of preterm birth: Guidelines for research. Am J Obstet Gynecol, , , 2006.

Sanada, H, Yatabe, J, Midorikawa, S, Hashimoto, S, Watanabe, T, Moore, JH, Ritchie, MD, Williams, SM, Pezzullo, JC, Sasaki, M, Eisner, GM, Jose, PA, Felder, RA. Single-Nucleotide Polymorphisms for Diagnosis of Salt-Sensitive Hypertension. Clin Chem, , , 2006.

Velez, DR, Guruju, M, Vinukonda, G, Prater, A, Kumar, A, Williams, SM. Angiotensinogen promoter sequence variants in essential hypertension. Am J Hypertens, 19(12), 1278-85, 2006.

Zhu, K, Hunter, S, Payne-Wilks, K, Sutcliffe, C, Bentley, C, Roland, CL, Williams, SM. Potential differences in breast cancer risk factors based on CYP1A1 MspI and African-American-specific genotypes. Ethn Dis, 16(1), 207-15, 2006.

Moore, JH, Williams, SM. Traversing the conceptual divide between biological and statistical epistasis: systems biology and a more modern synthesis. Bioessays, 27(6), 637-46, 2005.

Soares, ML, Coelho, T, Sousa, A, Batalov, S, Concei???#o, I, Sales-Lu?-s, ML, Ritchie, MD, Williams, SM, Nievergelt, CM, Schork, NJ, Saraiva, MJ, Buxbaum, JN. Susceptibility and modifier genes in Portuguese transthyretin V30M amyloid polyneuropathy: complexity in a single-gene disease. Hum Mol Genet, 14(4), 543-53, 2005.

Coffey, Christopher S, Hebert, Patricia R, Krumholz, Harlan M, Morgan, Thomas M, Williams, Scott M, Moore, Jason H. Reporting of model validation procedures in human studies of genetic interactions. Nutrition, 20(1), 69-73, 2004.

Robinson, M, Williams, SM. Role of two angiotensinogen polymorphisms in blood pressure variation. J Hum Hypertens, 18(12), 865-9, 2004.

Smith, MW, Patterson, N, Lautenberger, JA, Truelove, AL, McDonald, GJ, Waliszewska, A, Kessing, BD, Malasky, MJ, Scafe, C, Le, E, De Jager, PL, Mignault, AA, Yi, Z, De The, G, Essex, M, Sankale, JL, Moore, JH, Poku, K, Phair, JP, Goedert, JJ, Vlahov, D, Williams, SM, Tishkoff, SA, Winkler, CA, De La Vega, FM, Woodage, T, Sninsky, JJ, Hafler, DA, Altshuler, D, Gilbert, DA, O''Brien, SJ, Reich, D. A high-density admixture map for disease gene discovery in african americans. Am J Hum Genet, 74(5), 1001-13, 2004. PMCID:1181963

Williams, Scott M, Haines, Jonathan L, Moore, Jason H. The use of animal models in the study of complex disease: all else is never equal or why do so many human studies fail to replicate animal findings. Bioessays, 26(2), 170-9, 2004.

Williams, Scott M, Ritchie, Marylyn D, Phillips, John A, Dawson, Elliot, Prince, Melissa, Dzhura, Elvira, Willis, Alecia, Semenya, Amma, Summar, Marshall, White, Bill C, Addy, Jonathan H, Kpodonu, John, Wong, Lee-Jun, Felder, Robin A, Jose, Pedro A, Moore, Jason H. Multilocus analysis of hypertension: a hierarchical approach. Hum Hered, 57(1), 28-38, 2004.

Williams, SM, Templeton, AR. Race and genomics. N Engl J Med, 348(25), 2581-2; author reply 2581-2, 2003.

Zhu, K, Davidson, NE, Hunter, S, Yang, X, Payne-Wilks, K, Roland, CL, Phillips, D, Bentley, C, Dai, M, Williams, SM. Methyl-group dietary intake and risk of breast cancer among African-American women: a case-control study by methylation status of the estrogen receptor alpha genes. Cancer Causes Control, 14(9), 827-36, 2003.

Bengra, Chikh, Mifflin, Theodore E, Khripin, Yuri, Manunta, Paolo, Williams, Scott M, Jose, Pedro A, Felder, Robin A. Genotyping of essential hypertension single-nucleotide polymorphisms by a homogeneous PCR method with universal energy transfer primers. Clin Chem, 48(12), 2131-40, 2002.

Engert, James C, Vohl, Marie-Claude, Williams, Scott M, Lepage, Pierre, Loredo-Osti, J C, Faith, Janet, Dor??, Carole, Renaud, Yannick, Burtt, No?

Felder, RA, Sanada, H, Xu, J, Yu, PY, Wang, Z, Watanabe, H, Asico, LD, Wang, W, Zheng, S, Yamaguchi, I, Williams, SM, Gainer, J, Brown, NJ, Hazen-Martin, D, Wong, LJ, Robillard, JE, Carey, RM, Eisner, GM, Jose, PA. G protein-coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl Acad Sci U S A, 99(6), 3872-7, 2002. PMCID:122616

Moore, Jason H, Williams, Scott M. New strategies for identifying gene-gene interactions in hypertension. Ann Med, 34(2), 88-95, 2002.

Tarumi, Takashi, Kravtsov, Dmitri V, Zhao, Mingming, Williams, Scott M, Gailani, David. Cloning and characterization of the human factor XI gene promoter: transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha ) is required for hepatocyte-specific expression of factor XI. J Biol Chem, 277(21), 18510-6, 2002.

Tishkoff, Sarah A, Williams, Scott M. Genetic analysis of African populations: human evolution and complex disease. Nat Rev Genet, 3(8), 611-21, 2002.

Tishkoff, SA, Varkonyi, R, Cahinhinan, N, Abbes, S, Argyropoulos, G, Destro-Bisol, G, Drousiotou, A, Dangerfield, B, Lefranc, G, Loiselet, J, Piro, A, Stoneking, M, Tagarelli, A, Tagarelli, G, Touma, EH, Williams, SM, Clark, AG. Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science, 293(5529), 455-62, 2001.

Tarumi, T, Martincic, D, Whitlock, J A, Addy, J H, Williams, S M, Gailani, D. Conserved worldwide linkage disequilibrium in the human factor XI gene. Genomics, 70(2), 269-72, 2000.

Williams, S M, Addy, J H, Phillips, J A, Dai, M, Kpodonu, J, Afful, J, Jackson, H, Joseph, K, Eason, F, Murray, M M, Epperson, P, Aduonum, A, Wong, L J, Jose, P A, Felder, R A. Combinations of variations in multiple genes are associated with hypertension. Hypertension, 36(1), 2-6, 2000.

Zhu, K, Williams, S M. Methyl-deficient diets, methylated ER genes and breast cancer: an hypothesized association. Cancer Causes Control, 9(6), 615-20, 1998.

Zhu, K, Bernard, L J, Levine, R S, Williams, S M. Estrogen receptor status of breast cancer: a marker of different stages of tumor or different entities of the disease. Med Hypotheses, 49(1), 69-75, 1997.

Williams, S.M. and S. Sarkar. Assortative mating and the adaptive landscape. Evolution , 48, 868 875, 1994.

Scott, MP, Williams, SM. Comparative reproductive success of communally breeding burying beetles as assessed by PCR with randomly amplified polymorphic DNA. Proc Natl Acad Sci U S A, 90(6), 2242-5, 1993. PMCID:46062

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