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.
Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver.
(2014 Oct) Hum Mol Genet
. 2014 Oct 15;23(20):5558-69. doi: 10.1093/hmg/ddu268. Epub 2014 May 30. 24879639
pRRophetic: An R Package for Prediction of Clinical Chemotherapeutic Response from Tumor Gene Expression Levels.
(2014) PLoS One
. 2014 Sep 17;9(9):e107468. doi: 10.1371/journal.pone.0107468. eCollection 2014. 25229481
Integrative analyses of genetic variation, epigenetic regulation, and the transcriptome to elucidate the biology of platinum sensitivity.
(2014) BMC Genomics
. 2014 Apr 16;15:292. doi: 10.1186/1471-2164-15-292. 24739237
Genome-wide Interrogation of Longitudinal FEV1 in Children with Asthma.
(2014 Sep) Am J Respir Crit Care Med
. 2014 Sep 15;190(6):619-27. doi: 10.1164/rccm.201403-0460OC. 25221879
Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD.
(2014 Aug) Am J Psychiatry
. 2014 Aug 26. doi: 10.1176/appi.ajp.2014.13101306. 25158072
Genetic association signal near NTN4 in Tourette syndrome.
(2014 Aug) Ann Neurol
. 2014 Aug;76(2):310-5. doi: 10.1002/ana.24215. Epub 2014 Jul 21. 25042818
Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.
(2014 Aug) J Am Acad Child Adolesc Psychiatry
. 2014 Aug;53(8):910-9. doi: 10.1016/j.jaac.2014.04.022. Epub 2014 Jun 24. 25062598
Poly-omic prediction of complex traits: OmicKriging.
(2014 Jul) Genet Epidemiol
. 2014 Jul;38(5):402-15. doi: 10.1002/gepi.21808. Epub 2014 May 2. 24799323
Re: Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA.
(2014 May) J Natl Cancer Inst
. 2014 Apr 3;106(5). pii: dju063. doi: 10.1093/jnci/dju063. 24700804
Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder.
(2014 Apr) Proc Natl Acad Sci U S A
. 2014 Apr 22;111(16):5968-73. doi: 10.1073/pnas.1318810111. Epub 2014 Apr 7. 24711425
Genome-wide association study of Tourette's syndrome.
(2013 Jun) Mol Psychiatry
. 2013 Jun;18(6):721-8. doi: 10.1038/mp.2012.69. Epub 2012 Aug 14. 22889924
Enrichment of cis-regulatory gene expression SNPs and methylation quantitative trait loci among bipolar disorder susceptibility variants.
(2013 Mar) Mol Psychiatry
. 2013 Mar;18(3):340-6. doi: 10.1038/mp.2011.174. Epub 2012 Jan 3. 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.
(2012) Mol Autism
. 2012 May 16;3(1):3. doi: 10.1186/2040-2392-3-3. 22591576
Variants affecting exon skipping contribute to complex traits.
(2012) PLoS genetics (in press)
Genetic architecture of microRNA expression: implications for the transcriptome and complex traits.
(2012 Jun) Am J Hum Genet
. 2012 Jun 8;90(6):1046-63. doi: 10.1016/j.ajhg.2012.04.023. Epub 2012 May 31. 22658545
A genome-wide association study of overall survival in pancreatic cancer patients treated with gemcitabine in CALGB 80303.
(2012 Jan) Clin Cancer Res
. 2012 Jan 15;18(2):577-84. doi: 10.1158/1078-0432.CCR-11-1387. Epub 2011 Dec 5. 22142827
Germline BAP1 mutations predispose to malignant mesothelioma.
(2011 Oct) Nat Genet
. 2011 Aug 28;43(10):1022-5. doi: 10.1038/ng.912. 21874000
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.
(2011 Aug) Diabetologia
. 2011 Aug;54(8):2047-55. doi: 10.1007/s00125-011-2188-3. Epub 2011 Jun 7. 21647700
Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS.
(2010 Apr) PLoS Genet
. 2010 Apr 1;6(4):e1000888. doi: 10.1371/journal.pgen.1000888. 20369019