Research Description

The Cox Lab conducts research to identify and characterize the genetic component to common diseases and complex human traits.   Our lab is computational and “dry” rather than a traditional molecular genetics (“wet”) laboratory.  We develop methods to analyze and integrate a wide variety of data types and then apply these methods to analyze data from many different diseases and phenotypes.  For example, we are currently funded to analyze RNAseq data generated through the GTEx (Genotype-Tissue Expression) project (http://commonfund.nih.gov/GTEx/), as well as sequence data generated through the 1000 Genomes Project.  Our lab was the first to show that the genetic variation associated with complex human phenotypes is much more likely than expected to be variation that is also associated with mRNA levels for human transcripts¹ – i.e. that SNPs associated with human diseases are also likely to be eQTLs (expression quantitative trait loci).  More recently, we have also shown that SNPs associated with microRNA levels² and alternative splicing are over-represented among SNPs associated with human diseases³.  We are utilizing this information to develop new gene-based methods for genome association analysis that allow us to place more weight on genetic variation for which we have prior evidence of function.

We work extensively in pharmacogenomics on research projects designed to identify the genetic basis of response to chemotherapeutic agents and adverse events⁴.  We also have a long history of conducting research on the genetics of type 2 diabetes⁵, and are currently analyzing sequence data generated for the T2DGENES project – more than 10,000 exomes, and 600 whole genomes (60X coverage).  We are also part of the University of Chicago Conte Center, focused on applying new approaches to understand the genetic basis of autism, bipolar disorder and schizophrenia.^6,7 I lead the analytic group for the International Tourette Syndrome Consortium, where we are conducting analyses for both GWAS (genome-wide association studies)⁸, and sequencing studies.  We are also working on breast cancer using both GWAS and sequence data, and have had recent success in characterizing genetic risk factors for mesothelioma⁹.

Selected Publications

Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS.

Nicolae DL, Gamazon E, Zhang W, Duan S, Dolan ME, Cox NJ

(Apr 2010) PLoS genetics 6(4):e1000888 PMID:20369019 (Full Text)

Genetic architecture of microRNA expression: implications for the transcriptome and complex traits.

Gamazon ER, Ziliak D, Im HK, LaCroix B, Park DS, Cox NJ, Huang RS

(Jun 2012) American journal of human genetics 90(6):1046-63 PMID:22658545 (Full Text)

Variants affecting exon skipping contribute to complex traits.

Lee, Y, Gamazon ER, Rebman E, Lee Y, Lee, S, Dolan ME, Cox NJ, Lussier YA

(2012) PLoS genetics (in press)

A genome-wide association study of overall survival in pancreatic cancer patients treated with gemcitabine in CALGB 80303.

Innocenti F, Owzar K, Cox NL, Evans P, Kubo M, Zembutsu H, Jiang C, Hollis D, Mushiroda T, Li L, Friedman P, Wang L, Glubb D, Hurwitz H, Giacomini KM, McLeod HL, Goldberg RM, Schilsky RL, Kindler HL, Nakamura Y, Ratain MJ

(Jan 2012) Clinical cancer research : an official journal of the American Association for Cancer Research 18(2):577-84 PMID:22142827 (Full Text)

Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals.

Below JE, Gamazon ER, Morrison JV, Konkashbaev A, Pluzhnikov A, McKeigue PM, Parra EJ, Elbein SC, Hallman DM, Nicolae DL, Bell GI, Cruz M, Cox NJ, Hanis CL

(Aug 2011) Diabetologia 54(8):2047-55 PMID:21647700

Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants.

Gamazon ER, Badner JA, Cheng L, Zhang C, Zhang D, Cox NJ, Gershon ES, Kelsoe JR, Greenwood TA, Nievergelt CM, Chen C, McKinney R, Shilling PD, Schork NJ, Smith EN, Bloss CS, Nurnberger JI, Edenberg HJ, Foroud T, Koller DL, Scheftner WA, Coryell W, Rice J, Lawson WB, Nwulia EA, Hipolito M, Byerley W, McMahon FJ, Schulze TG, Berrettini WH, Potash JB, Zandi PP, Mahon PB, McInnis MG, Zöllner S, Zhang P, Craig DW, Szelinger S, Barrett TB, Liu C

(Jan 2012) Molecular psychiatry PMID:22212596

Loci nominally associated with autism from genome-wide analysis show enrichment of brain expression quantitative trait loci but not lymphoblastoid cell line expression quantitative trait loci.

Davis LK, Gamazon ER, Kistner-Griffin E, Badner JA, Liu C, Cook EH, Sutcliffe JS, Cox NJ

(May 2012) Molecular autism 3(1):3 PMID:22591576

Genome-wide association study of Tourette's syndrome.

Scharf JM, Yu D, Mathews CA, Neale BM, Stewart SE, Fagerness JA, Evans P, Gamazon E, Edlund CK, Service SK, Tikhomirov A, Osiecki L, Illmann C, Pluzhnikov A, Konkashbaev A, Davis LK, Han B, Crane J, Moorjani P, Crenshaw AT, Parkin MA, Reus VI, Lowe TL, Rangel-Lugo M, Chouinard S, Dion Y, Girard S, Cath DC, Smit JH, King RA, Fernandez TV, Leckman JF, Kidd KK, Kidd JR, Pakstis AJ, State MW, Herrera LD, Romero R, Fournier E, Sandor P, Barr CL, Phan N, Gross-Tsur V, Benarroch F, Pollak Y, Budman CL, Bruun RD, Erenberg G, Naarden AL, Lee PC, Weiss N, Kremeyer B, Berrío GB, Campbell DD, Cardona Silgado JC, Ochoa WC, Mesa Restrepo SC, Muller H, Valencia Duarte AV, Lyon GJ, Leppert M, Morgan J, Weiss R, Grados MA, Anderson K, Davarya S, Singer H, Walkup J, Jankovic J, Tischfield JA, Heiman GA, Gilbert DL, Hoekstra PJ, Robertson MM, Kurlan R, Liu C, Gibbs JR, Singleton A, Hardy J, Strengman E, Ophoff RA, Wagner M, Moessner R, Mirel DB, Posthuma D, Sabatti C, Eskin E, Conti DV, Knowles JA, Ruiz-Linares A, Rouleau GA, Purcell S, Heutink P, Oostra BA, McMahon WM, Freimer NB, Cox NJ, Pauls DL

(Aug 2012) Molecular psychiatry PMID:22889924

Germline BAP1 mutations predispose to malignant mesothelioma.

Testa JR, Cheung M, Pei J, Below JE, Tan Y, Sementino E, Cox NJ, Dogan AU, Pass HI, Trusa S, Hesdorffer M, Nasu M, Powers A, Rivera Z, Comertpay S, Tanji M, Gaudino G, Yang H, Carbone M

(Oct 2011) Nature genetics 43(10):1022-5 PMID:21874000 (Full Text)