Stephen S. Rich
Harrison Professor of Public Health Sciences and
Biochemistry & Molecular Genetics
Ph.D., Purdue University
Genetic Epidemiology


We are interested in the genetic basis of complex human disease, using genetic/genomic approaches coupled with statistical genetic, genetic epidemiologic and bioinformatics methods to more fully discover causal genes that can be functionally characterized. Our research uses genome-wide approaches to identify loci in the human genome that then require more detailed interrogation to establish putative candidate genes, and the variants in the genes that contribute to disease risk. Our primary diseases of interest are type 1 diabetes, diabetic nephropathy (kidney disease), autoimmunity, atherosclerosis, cardiovascular and cerebrovascular diseases.

The genomic technologies (both laboratory and analytic) have rapidly evolved over the past decade. Our studies have included family-based, case-control and cohort collections. Our approaches have included genome-wide linkage, association, fine-mapping, targeted sequencing and exome sequencing. Functional approaches have now expanded to RNAseq and characterization of specific genes by using targeted assays and model systems. Collaborations are typical of our work, including the NIDDK/JDRF Type 1 Diabetes Genetics Consortium (T1DGC), the NHLBI Exome Sequencing Project (ESP), and the NHLBI Multi-Ethnic Study of Atherosclerosis (MESA). Our current work addresses the need to better understand the complex genetic architecture of common human disease from genomic diversity and how this diversity interacts with environmental risk factors to define a risk profile for a variety of disorders.

Selected References

Hunt KA, Mistry V, Bockett NA, Ahmad T, Ban M, Barker JN, Barrett JC, BlackburnH, Brand O, Burren O, Capon F, Compston A, Gough SC, Jostins L, Kong Y, Lee JC,Lek M, MacArthur DG, Mansfield JC, Mathew CG, Mein CA, Mirza M, Nutland S,Onengut-Gumuscu S, Papouli E, Parkes M, Rich SS, Sawcer S, Satsangi J, SimmondsMJ, Trembath RC, Walker NM, Wozniak E, Todd JA, Simpson MA, Plagnol V, van HeelDA. (2013) "Negligible impact of rare autoimmune-locus coding-region variants on missing heritability." Nature. Jun 498(7453):232-5. doi: 10.1038/nature12170. Epub 2013 May 22. [PubMed]

Ferreira RC, Freitag DF, Cutler AJ, Howson JM, Rainbow DB, Smyth DJ, Kaptoge S,Clarke P, Boreham C, Coulson RM, Pekalski ML, Chen WM, Onengut-Gumuscu S, RichSS, Butterworth AS, Malarstig A, Danesh J, Todd JA. (2013) "Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases." PLoS Genet. 9:e1003444. doi: 10.1371/journal.pgen.1003444. Epub 2013 Apr 4. [PubMed]

Erlich HA, Valdes AM, McDevitt SL, Simen BB, Blake LA, McGowan KR, Todd JA, Rich SS, Noble JA; Type 1 Diabetes Genetics Consortium (T1DGC). (2013) "Next Generation Sequencing Reveals the Association of DRB3*02:02 With Type 1 Diabetes." Diabetes. 62:2618-22. doi: 10.2337/db12-1387. Epub 2013 Mar 5. [PubMed]

Caramori ML, Kim Y, Moore JH, Rich SS, Mychaleckyj JC, Kikyo N, Mauer M. (2012) "Gene expression differences in skin fibroblasts in identical twins discordant for type 1 diabetes." Diabetes. 61:739-44. doi: 10.2337/db11-0617. Epub 2012 Feb 7. [PubMed]

Auer PL, Johnsen JM, Johnson AD, Logsdon BA, Lange LA, Nalls MA, Zhang G,Franceschini N, Fox K, Lange EM, Rich SS, O'Donnell CJ, Jackson RD, Wallace RB,Chen Z, Graubert TA, Wilson JG, Tang H, Lettre G, Reiner AP, Ganesh SK, Li Y. (2012) "Imputation of exome sequence variants into population- based samples and blood-cell-trait-associated loci in African Americans: NHLBI GO Exome Sequencing Project." Am J Hum Genet. Nov 91:794-808. doi: 10.1016/j.ajhg.2012.08.031. Epub2012 Oct 25. [PubMed]

Caramori ML, Kim Y, Moore JH, Rich SS, Mychaleckyj JC, Kikyo N, Mauer M. (2012) "Gene expression differences in skin fibroblasts in identical twins discordant for type 1 diabetes." Diabetes. 61:739-44. doi: 10.2337/db11-0617. Epub 2012 Feb 7. [PubMed]

Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, Abecasis GR,Barrett JC, Behrens T, Cho J, De Jager PL, Elder JT, Graham RR, Gregersen P,Klareskog L, Siminovitch KA, van Heel DA, Wijmenga C, Worthington J, Todd JA,Hafler DA, Rich SS, Daly MJ; FOCiS Network of Consortia. (2011) "Pervasive sharing of genetic effects in autoimmune disease." PLoS Genet. 7:e1002254. doi: 10.1371/journal.pgen.1002254. Epub 2011 Aug 10. [PubMed]

Figler RA, Wang G, Srinivasan S, Jung DY, Zhang Z, Pankow JS, Ravid K, FredholmB, Hedrick CC, Rich SS, Kim JK, LaNoue KF, Linden J. (2011) "Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans." Diabetes. 60:669-79. doi: 10.2337/db10-1070. [PubMed]

Meschia JF, Nalls M, Matarin M, Brott TG, Brown RD Jr, Hardy J, Kissela B, RichSS, Singleton A, Hernandez D, Ferrucci L, Pearce K, Keller M, Worrall BB;Siblings With Ischemic Stroke Study Investigators. (2011) "Siblings with ischemic stroke study: results of a genome-wide scan for stroke loci." Stroke. 42(10):2726-32. doi: 10.1161/STROKEAHA.111.620484. Epub 2011 Sep22. [PubMed]

Palmer ND, Langefeld CD, Ziegler JT, Hsu F, Haffner SM, Fingerlin T, Norris JM,Chen YI, Rich SS, Haritunians T, Taylor KD, Bergman RN, Rotter JI, Bowden DW. (2010) "Candidate loci for insulin sensitivity and disposition index from a genome-wide association analysis of Hispanic participants in the Insulin Resistance Atherosclerosis (IRAS) Family Study." Diabetologia. 53:281-9. doi: 10.1007/s00125-009-1586-2. Epub 2009 Nov10. [PubMed]

Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C,Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ,Stevens H, Todd JA, Walker NM, Rich SS; Type 1 Diabetes Genetics Consortium. (2009) "Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes." Nat Genet. 41:703-7. doi: 10.1038/ng.381. Epub 2009 May 10. [PubMed]