Stephen S. Rich

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Primary Appointment

Professor, Public Health Sciences

Education

  • PhD, Genetics, Purdue University

Research Disciplines

Bioinformatics and Genomics, Biology, Cardiovascular Biology, Epigenetics, Genetics, Immunology, Translational Science

Research Interests

Genetic basis of common human disease, including type 1 diabetes, diabetic complications, ischemic stroke, atherosclerosis

Research Description

Dr. Rich's research is centered on understanding the genetic epidemiology of complex human disease, including the genes contributing to atherosclerosis, stroke and intermediate phenotypes (risk factors). These studies range from estimating the familial aggregation of disease and subclinical markers of disease within families, to gene mapping, gene discovery and functional significance of the gene variants. In the realm of atherosclerosis and risk factors, the primary study population is the Multi-Ethnic Study of Atherosclerosis (MESA), a collection of ~6,000 adults (aged 45+) without evidence of clinical disease. These subjects (Caucasian, African-American, Hispanic-American, Chinese-American) have extensive imaging, biomarker and clinical longitudinal data, as well as DNA for genetic studies. Currently, over 200 candidate genes related to atherosclerosis are being assessed, and both a genome-wide association scan (1 million SNPs) and linkage scan (6K SNPs in families) are being used to discover new genes and pathways. Examination of the genetic contribution to risk of ischemic stroke is the primary focus of the Siblings With Ischemic Stroke Study (SWISS) and the Ischemic Stroke Genetic Study (ISGS). Family-based linkage (SWISS), candidate gene (SWISS, ISGS) and genome-wide association (ISGS) methods have been utilized to detect stroke susceptibility genes. A primary goal of these research efforts is to identify novel genes and pathways that can serve a predictors of risk, identify those at highest risk of disease and, therefore, amenable to intervention, and to develop models of disease through manipulation of these genes and thus identify potential therapeutic targets.

Personal Statement

Dr. Rich's research is centered on understanding the genetic epidemiology of complex human disease, including the genes contributing to atherosclerosis, stroke and intermediate phenotypes (risk factors). These studies range from estimating the familial aggregation of disease and subclinical markers of disease within families, to gene mapping, gene discovery and functional significance of the gene variants. In the realm of atherosclerosis and risk factors, the primary study population is the Multi-Ethnic Study of Atherosclerosis (MESA), a collection of ~6,000 adults (aged 45+) without evidence of clinical disease. These subjects (Caucasian, African-American, Hispanic-American, Chinese-American) have extensive imaging, biomarker and clinical longitudinal data, as well as DNA for genetic studies. Currently, over 200 candidate genes related to atherosclerosis are being assessed, and both a genome-wide association scan (1 million SNPs) and linkage scan (6K SNPs i n families) are being used to discover new genes and pathways. Examination of the genetic contribution to risk of ischemic stroke is the primary focus of the Siblings With Ischemic Stroke Study (SWISS) and the Ischemic Stroke Genetic Study (ISGS). Family-based linkage  (SWISS), candidate gene (SWISS, ISGS) and genome-wide association (ISGS) methods have been utilized to detect stroke susceptibility genes. A primary goal of these research efforts is to identify novel genes and pathways that can serve a predictors of risk, identify those at highest risk of disease and, therefore, amenable to intervention, and to develop models of disease through manipulation of these genes and thus identify potential therapeutic targets.

Training

  • Basic Cardiovascular Research Training Grant
  • Global Infectious Disease Research Training Grant at UVa

Selected Publications

Guan M, Keaton JM, Dimitrov L, Hicks PJ, Xu J, Palmer ND, Ma L, Das SK, Chen YI, Coresh J, Fornage M, Franceschini N, Kramer H, Langefeld CD, Mychaleckyj JC, Parekh RS, Post WS, Rasmussen-Torvik LJ, Rich SS, Rotter JI, Sedor JR, Thornley-Brown D, Tin A, Wilson JG, Freedman BI, Bowden DW, Ng MCY, Genome-wide association study identifies novel loci for type 2 diabetes-attributed end-stage kidney disease in African Americans., 2019; Human genomics. 13(1) 21. PMID: 31092297 | PMCID: PMC6521376

Salem RM, Todd JN, Sandholm N, Cole JB, Chen WM, Andrews D, Pezzolesi MG, McKeigue PM, Hiraki LT, Qiu C, Nair V, Di Liao C, Cao JJ, Valo E, Onengut-Gumuscu S, Smiles AM, McGurnaghan SJ, Haukka JK, Harjutsalo V, Brennan EP, van Zuydam N, Ahlqvist E, Doyle R, Ahluwalia TS, Lajer M, Hughes MF, Park J, Skupien J, Spiliopoulou A, Liu A, Menon R, Boustany-Kari CM, Kang HM, Nelson RG, Klein R, Klein BE, Lee KE, Gao X, Mauer M, Maestroni S, Caramori ML, de Boer IH, Miller RG, Guo J, Boright AP, Tregouet D, Gyorgy B, Snell-Bergeon JK, Maahs DM, Bull SB, Canty AJ, Palmer CNA, Stechemesser L, Paulweber B, Weitgasser R, Sokolovska J, RovÄ«te V, PÄ«rÄgs V, Prakapiene E, Radzeviciene L, Verkauskiene R, Panduru NM, Groop LC, McCarthy MI, Gu HF, Möllsten A, Falhammar H, Brismar K, Martin F, Rossing P, Costacou T, Zerbini G, Marre M, Hadjadj S, McKnight AJ, Forsblom C, McKay G, Godson C, Maxwell AP, Kretzler M, Susztak K, Colhoun HM, Krolewski A, Paterson AD, Groop PH, Rich SS, Hirschhorn JN, Florez JC, Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen., 2019; Journal of the American Society of Nephrology : JASN. 30(10) 2000-2016. PMID: 31537649 | PMCID: PMC6779358

Onengut-Gumuscu S, Chen WM, Robertson CC, Bonnie JK, Farber E, Zhu Z, Oksenberg JR, Brant SR, Bridges SL, Edberg JC, Kimberly RP, Gregersen PK, Rewers MJ, Steck AK, Black MH, Dabelea D, Pihoker C, Atkinson MA, Wagenknecht LE, Divers J, Bell RA, Erlich HA, Concannon P, Rich SS, Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score., 2019; Diabetes care. 42(3) 406-415. PMID: 30659077 | PMCID: PMC6385701

Hippich M, Beyerlein A, Hagopian WA, Krischer JP, Vehik K, Knoop J, Winker C, Toppari J, Lernmark Ã, Rewers MJ, Steck AK, She JX, Akolkar B, Robertson CC, Onengut-Gumuscu S, Rich SS, Bonifacio E, Ziegler AG, Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families., 2019; Diabetes. 68(4) 847-857. PMID: 30655385 | PMCID: PMC6425872

Sharp SA, Rich SS, Wood AR, Jones SE, Beaumont RN, Harrison JW, Schneider DA, Locke JM, Tyrrell J, Weedon MN, Hagopian WA, Oram RA, Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis., 2019; Diabetes care. 42(2) 200-207. PMID: 30655379 | PMCID: PMC6341291

Márquez A, Kerick M, Zhernakova A, Gutierrez-Achury J, Chen WM, Onengut-Gumuscu S, González-Ãlvaro I, Rodriguez-Rodriguez L, Rios-Fernández R, González-Gay MA, Mayes MD, Raychaudhuri S, Rich SS, Wijmenga C, Martín J, Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations., 2018; Genome medicine. 10(1) 97. PMID: 30572963 | PMCID: PMC6302306

Beyerlein A, Bonifacio E, Vehik K, Hippich M, Winkler C, Frohnert BI, Steck AK, Hagopian WA, Krischer JP, Lernmark Ã, Rewers MJ, She JX, Toppari J, Akolkar B, Rich SS, Ziegler AG, Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study., 2018; Journal of medical genetics. 56(9) 602-605. PMID: 30287597 | PMCID: PMC6690814

Westra HJ, Martínez-Bonet M, Onengut-Gumuscu S, Lee A, Luo Y, Teslovich N, Worthington J, Martin J, Huizinga T, Klareskog L, Rantapaa-Dahlqvist S, Chen WM, Quinlan A, Todd JA, Eyre S, Nigrovic PA, Gregersen PK, Rich SS, Raychaudhuri S, Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes., 2018; Nature genetics. 50(10) 1366-1374. PMID: 30224649 | PMCID: PMC6364548

Macri V, Brody JA, Arking DE, Hucker WJ, Yin X, Lin H, Mills RW, Sinner MF, Lubitz SA, Liu CT, Morrison AC, Alonso A, Li N, Fedorov VV, Janssen PM, Bis JC, Heckbert SR, Dolmatova EV, Lumley T, Sitlani CM, Cupples LA, Pulit SL, Newton-Cheh C, Barnard J, Smith JD, Van Wagoner DR, Chung MK, Vlahakes GJ, O'Donnell CJ, Rotter JI, Margulies KB, Morley MP, Cappola TP, Benjamin EJ, Muzny D, Gibbs RA, Jackson RD, Magnani JW, Herndon CN, Rich SS, Psaty BM, Milan DJ, Boerwinkle E, Mohler PJ, Sotoodehnia N, Ellinor PT, Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction., 2018; Circulation. Genomic and precision medicine. 11(5) e001663. PMID: 29752399 | PMCID: PMC6377236

Keaton JM, Gao C, Guan M, Hellwege JN, Palmer ND, Pankow JS, Fornage M, Wilson JG, Correa A, Rasmussen-Torvik LJ, Rotter JI, Chen YI, Taylor KD, Rich SS, Wagenknecht LE, Freedman BI, Ng MCY, Bowden DW, Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans., 2018; Genetic epidemiology. 42(6) 559-570. PMID: 29691896 | PMCID: PMC6160319

Bonifacio E, Beyerlein A, Hippich M, Winkler C, Vehik K, Weedon MN, Laimighofer M, Hattersley AT, Krumsiek J, Frohnert BI, Steck AK, Hagopian WA, Krischer JP, Lernmark Ã, Rewers MJ, She JX, Toppari J, Akolkar B, Oram RA, Rich SS, Ziegler AG, Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: A prospective study in children., 2018; PLoS medicine. 15(4) e1002548. PMID: 29614081 | PMCID: PMC5882115

Newman JRB, Conesa A, Mika M, New FN, Onengut-Gumuscu S, Atkinson MA, Rich SS, McIntyre LM, Concannon P, Disease-specific biases in alternative splicing and tissue-specific dysregulation revealed by multitissue profiling of lymphocyte gene expression in type 1 diabetes., 2017; Genome research. 27(11) 1807-1815. PMID: 29025893 | PMCID: PMC5668939

Hu X, Deutsch AJ, Lenz TL, Onengut-Gumuscu S, Han B, Chen WM, Howson JM, Todd JA, de Bakker PI, Rich SS, Raychaudhuri S, Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk., 2015; Nature genetics. 47(8) 898-905. PMID: 26168013 | PMCID: PMC4930791

Onengut-Gumuscu S, Chen WM, Burren O, Cooper NJ, Quinlan AR, Mychaleckyj JC, Farber E, Bonnie JK, Szpak M, Schofield E, Achuthan P, Guo H, Fortune MD, Stevens H, Walker NM, Ward LD, Kundaje A, Kellis M, Daly MJ, Barrett JC, Cooper JD, Deloukas P, Todd JA, Wallace C, Concannon P, Rich SS, Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers., 2015; Nature genetics. 47(4) 381-6. PMID: 25751624 | PMCID: PMC4380767