Leah C. Kottyan, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-1316

Email leah.kottyan@cchmc.org

Genetic basis of lupus; genetic basis of eosinophilic esophagitis; immunological mechanisms mediating genetic association with disease

Visit the Kottyan Lab.

For the past decade, many geneticists have approached genetic analysis with the idea that they simply need to increase statistical power by enlarging the sample size (e.g. ~100,000 person height GWAS) and assess enough loci in order to find the “genes” associated with a disease. Unfortunately, clinicians can do relatively little with this type of correlative genetic information. Dr. Kottyan recently lead a genome-wide association analysis of eosinophilic esophagitis in which they went beyond the identification of nine new risk loci and identified the molecular, tissue-specific mechanisms through which genetic variants at the CAPN14 locus increase risk of disease.

During her post-doctoral fellowship, she optimized statistical modeling strategies using genetic data from large multi-ancestral cohorts to identify candidate genetic causal variants through complementary frequentist and Bayesian approaches. In genetic analysis, it is easy and even tempting to make a story out of a genetic variant that seems important. Using two types of statistical analyses on multiple cohorts of different ancestry helps to avoid the misplaced attribution of causality. Instead, Dr. Kottyan’s group develops a short list of variants that are most statistically likely to be causal before they start biological or functional analysis. Once identified, the group predicts and confirms biological phenotypes that are affected by the risk variants.

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

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

View PubMed Publications

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 L. Lupus risk-variant increases pSTAT1 binding and decreases ETS1 expression. American journal of human genetics. 2015.

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, Weirauch MT, Rothenberg ME. Making it Big in Allergy. J Allergy Clin Immunol. 2015 Jan;135(1):43-5.

Makashir SB, Kottyan LC, Weirauch MT. Meta-analysis of Differential Gene Co-expression: Application to Lupus. Pacific Symposium on Biocomputing Proceedings. 2015.

Brungs L, Lele A, Kottyan L, Levy B, Moncrieffe H. Genetic Basis of Rheumatic Diseases and the Importance of GWAS in Paediatric Rheumatology. Annals of Pediatric Rheumatology. 2015;3(3):105-115.

Verma SS, de Andrade M, Tromp G, Kuivaniemi H, Pugh E, Namjou-Khales B, Mukherjee S, Jarvik GP, Kottyan LC, Burt A, Bradford Y, Armstrong GD, Derr K, Crawford DC, Haines JL, Li R, Crosslin D, Ritchie MD. Imputation and quality control steps for combining multiple genome-wide datasets. Frontiers in Genetics. 2014 Dec 11;5:370.

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. Hum Mol Genet. 2014 Jan 15;24(2):582-98.

Namjou B, Ni Y, Harley IT, Chepelev I, Cobb B, Kottyan LC, Gaffney PM, Guthridge JM, Kaufman K, Harley JB. The effect of inversion at 8p23 on BLK association with lupus in Caucasian population. PLoS One. 2014 Dec 29;9(12):e115614.

Alexander ES, Martin LJ, Collins MH, Kottyan LC, Sucharew H, He H, Mukkada VA, Succop PA, Abonia JP, Foote H, Eby MD, Grotjan TM, Greenler AJ, Dellon ES, Demain JG, Furuta GT, Gurian LE, Harley JB, Hopp RJ, Kagalwalla A, Kaul A, Nadeau KC, Noel RJ, Putnam PE, von Tiehl KF, Rothenberg ME. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis. J Allergy Clin Immunol. 2014 Nov;134(5):1084-1092.

Fardo DW, Zhang X, Ding L, He H, Kurowski B, Alexander ES, Baye TM, Pilipenko V, Kottyan L, Nandakumar K, Martin LJ. On Family-based Genome-wide Association Studies with Large Pedigrees: Observations and Recommendations. BMC Proceedings. 2014;8(1):s26-s26.