A photo of Leah Kottyan.

Assistant Professor, UC Department of Pediatrics


My Biography & Research


Why do some individuals develop disease? Broadly speaking, genetic risk polymorphisms and environmental exposures act in concert with stochastic factors to influence risk for many diseases. Recent studies are beginning to identify the disease mechanisms impacted by specific genetic risk variants and environmental exposures. In particular, functional genomics-based approaches are revealing that changes in human chromatin state and gene expression are important molecular mechanisms through which genetic and environmental factors influence human disease risk. Understanding disease mechanisms is vitally important for the development of treatments and therapies. In the past two decades, thousands of genetic variants with roles in >1,500 human diseases have been identified. Importantly, genetic association studies do not identify causal SNPs, critical genes, or etiological pathways. There is a pressing need for new approaches that translate the massive results from genetic studies into clear mechanistic understandings of the genetic and environmental contributions to human diseases.

Dr. Kottyan's work in the Center for Autoimmune Genomics and Etiology (CAGE) focuses on identifying the molecular mechanisms that drive genetic associations of DNA risk loci with diseases that have an immunological component, especially Eosinophilic Esophagitis (EoE), Atopic Dermatitis (AD), and systemic lupus erythematosus (SLE or lupus). They use both Bayesian and frequentist approaches to identify the variants most likely to be causal for disease risk. Next, they turn to biological assays to identify genotype-dependent (allelic) differences in transcription factor binding, DNA regulatory activity, epigenetic regulation, and mRNA and protein expression in the context of allergic inflammation.

Research Interests

Genetic etiology; genotype-dependent mechanisms of gene regulation; eosinophilic esophagitis; systemic lupus erethematosus; atopic dermatitis

Academic Affiliation

Assistant Professor, UC Department of Pediatrics


Cincinnati Center for Eosinophilic Disorders, Cincinnati Center for Eosinophilic Disorders Research

My Education

BA: Chemistry and Cell Biology, Huntingdon College, Montgomery, AL, 2005.

PhD: Immunobiology, University of Cincinnati, Cincinnati, OH, 2010.

My Publications

Miller DE, Forney C, Rochman M, Cranert S, Habel J, Rymer J, Lynch A, Schroeder C, Lee J, Sauder A, Smith Q, Chawla M, Trimarchi MP, Lu X, Fjellman E, Brusilovsky M, Barski A, Waggoner S, Weirauch MT, Rothenberg ME, Kottyan LC. Genetic, Inflammatory, and Epithelial Cell Differentiation Factors Control Expression of Human Calpain-14. G3 (Bethesda). 2019 Mar 7;9(3):729-736.

Kottyan LC, Maddox A, Braxton JR, Stucke EM, Mukkada V, Putnam PE, Abonia JP, Chehade M, Wood RA, Pesek RD, Vickery BP, Furuta GT, Dawson P, Sampson HA, Martin LJ, Kelly JA, Kimberly RP, Sivils K, Gaffney PM, Kaufman K, Harley JB, Rothenberg ME. Genetic Variants at the 16p13 Locus Confer Risk for Eosinophilic Esophagitis. Genes and Immunity. 2018 Jun 8.

Patel Z, Lu X, Miller D, Forney CR, Lee J, Lynch A, Schroeder C, Parks L, Magnusen AF, Chen X, Pujato M, Maddox A, Zoller EE, Namjou B, Brunner HI, Henrickson M, Huggins JL, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath SK, Stevens AM, Freedman BI, Pons-Estel BA, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Martin J, Reveille JD, Anaya JM, James JA, Sivils KL, Criswell LA, Vilá LM, Petri M, Scofield RH, Kimberly RP, Edberg JC, Ramsey-Goldman R, Bang SY, Lee HS, Bae SC, Boackle SA, Cunninghame Graham D, Vyse TJ, Merrill JT, Niewold TB, Ainsworth HC, Silverman ED, Weisman MH, Wallace DJ, Raj P, Guthridge JM, Gaffney PM, Kelly JA, Alarcón-Riquelme ME, Langefeld CD, Wakeland EK, Kaufman KM, Weirauch MT, Harley JB, Kottyan LC. A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus. Human Molecular Genetics. 2018 Apr 18.

JB Harley*, X Chen, M Pujato, D Miller, A Maddox, C Forney, AF Magnusen, A Lynch, K Chetal, M Yukawa, A Barski, N Salomonis, KM Kaufman, LC Kottyan*, MT Weirauch*. Transcription factors operate across disease loci: EBNA2 in autoimmunity. Nature Genetics. 2018 Apr 16. *Co-corresponding author with Drs. Harley and Weirauch.

Zhang G, Feenstra B, Bacelis J, Liu X, Muglia LM, Juodakis J, Miller DE, Litterman N, Jiang PP, Russell L, Hinds DA, Hu Y, Weirauch MT, Chen X, Chavan AR, Wagner GP, Pavličev M, Nnamani MC, Maziarz J, Karjalainen MK, Rämet M, Sengpiel V, Geller F, Boyd HA, Palotie A, Momany A, Bedell B, Ryckman KK, Huusko JM, Forney CR, Kottyan LC, Hallman M, Teramo K, Nohr EA, Davey Smith G, Melbye M, Jacobsson B, Muglia LJ. Genetic Associations with Gestational Length and Spontaneous Preterm Birth. New England Journal of Medicine. 2017 Sep 21;377(12):1156-1167.

Lu X, Zoller EE, Weirauch M, Wu X, Namjou-Khales B, Williams A, Ziegler J, Comeau MR, Marion M, Glenn S, Adler A, Shen N, Nath SK, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown E, Gilkeson G, Alarcon GS, Reveille JD, Anaya JM, James JA, Sivils K, Criswell LA, Vila LM, Alarcon-Riquelme M, Petri M, Scofield RH, Kimberly R, Ramsey-Goldman R, Joo YB, Choi J, Bae SC, Boackle SA, Cunninghame-Graham DS, Vyse T, Guthridge JM, Gaffney PM, Langefeld CD, Kelly J, Greis K, Kaufman K, Harley JB, Kottyan LC. Lupus risk-variant increases pSTAT1 binding and decreases ETS1 expression. American Journal of Human Genetics. 2015 May 7;96(5):731-9.

Vaughn SE, Foley C, Lu X, Patel ZH, Zoller EE, Magnusen AF, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath S, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Reveille JD, Anaya J-M, James JA, Moser KL, Criswell LA, Vilá LM, Alarcón-Riquelme ME, Petri M, Scofield RH, Kimberly RP, Ramsey-Goldman R, Binjoo Y, Choi J, Bae S-C, Boackle SA, Vyse TJ, Guthridge JM, Namjou B, Gaffney PM, Langefeld CD, Kaufman KM, Kelly JA, Harley ITW, Harley JB, Kottyan LC. Lupus risk variants in the PXK locus alter B-cell receptor internalization. Frontiers in Genetics. 2015 Jan 8;5:450.

Kottyan LC, Zoller EE, Bene J, Lu X, Kelly JA, Rupert AM, Lessard CJ, Vaughn SE, Marion M, Weirauch MT, Namjou B, Adler A, Rasmussen A, Glenn S, Montgomery CG, Hirschfield GM, Xie G, Coltescu C, Amos C, Li H, Ice JA, Nath SK, Mariette X; Simon Bowman for UK primary Sjögren's syndrome registry, Rischmueller M, Lester S, Brun JG, Gøransson LG, Harboe E, Omdal R, Cunninghame-Graham DS, Vyse T, Miceli-Richard C, Brennan MT, Lessard JA, Wahren-Herlenius M, Kvarnström M, Illei GG, Witte T, Jonsson R, Eriksson P, Nordmark G; Wan-Fai Ng for UK primary Sjögren's syndrome registry, Anaya JM, Rhodus NL, Segal BM, Merrill JT, James JA, Guthridge JM, Scofield RH, Alarcon-Riquelme M, Bae SC, Boackle SA, Criswell LA, Gilkeson G, Kamen DL, Jacob CO, Kimberly R, Brown E, Edberg J, Alarcón GS, Reveille JD, Vilá LM, Petri M, Ramsey-Goldman R, Freedman BI, Niewold T, Stevens AM, Tsao BP, Ying J, Mayes MD, Gorlova OY, Wakeland W, Radstake T, Martin E, Martin J, Siminovitch K, Moser Sivils KL, Gaffney PM, Langefeld CD, Harley JB, Kaufman KM. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Human Molecular Genetics. 2014 Jan 15;24(2):582-98.

Kottyan LC, Davis BP, Sherrill JD, Liu K, Rochman M, Kaufman K, Weirauch MT, Vaughn S, Lazaro S, Rupert AM, Kohram M, Stucke EM, Kemme KA, Magnusen A, He H, Dexheimer P, Chehade M, Wood RA, Pesek RD, Vickery BP, Fleischer DM, Lindbad R, Sampson HA, Mukkada VA, Putnam PE, Abonia JP, Martin LJ, Harley JB, Rothenberg ME. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nature Genetics. 2014;46(8):895-900.

Kottyan LC, Patel ZH, Lazaro S, Williams MS, Ledbetter DH, Tromp H, Rupert A, Kohram M, Wagner M, Husami A, Qian Y, Valencia CA, Zhang K, Hostetter MK, Harley JB, Kaufman KM. The struggle to find reliable results in exome sequencing data: filtering out mendelian errors. Frontiers in Genetics. 2013;12;5:16.