Improved integrative framework combining association data with gene expression features to prioritize Crohn's disease genes

Human Molecular Genetics

Volumn 24, Issue 14, 2015, Pages 4147-4157

  Ning, Kaida ^a   Gettler, Kyle ^b   Zhang, Wei ^b   Ng, Sok Meng ^b   Bowen, B Monica ^b   Hyams, Jeffrey ^c   Stephens, Michael C ^d   Kugathasan, Subra ^e   Denson, Lee A ^f,g   Schadt, Eric E ^a   Hoffman, Gabriel E ^a   Cho, Judy H ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c Division of Pediatric Infectious Diseases   (United States)

^d MAYO CLINIC   (United States)

^e EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^g UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; MULTIPROTEIN COMPLEX;

ANTIGEN PRESENTATION; ARTICLE; AUTOIMMUNE DISEASE; CELL DIFFERENTIATION; CONTROLLED STUDY; CROHN DISEASE; GENE; GENE EXPRESSION; GENE LINKAGE DISEQUILIBRIUM; GENE LOCATION; GENE NUMBER; GENE ONTOLOGY; GENE OVEREXPRESSION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC MODEL; GENOME; HUMAN; HUMAN CELL; HUMAN TISSUE; IBD5 GENE; IMMUNITY; IMMUNOPATHOLOGY; IN VITRO STUDY; INFLAMMATION; MACROPHAGE; MEMORY T LYMPHOCYTE; MONOGENIC DISORDER; PATHOGENESIS; PATHOGENICITY; POLARIZATION; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; RECEIVER OPERATING CHARACTERISTIC; SCORING SYSTEM; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE ACTIVATION; TH17 CELL; UPREGULATION; CASE CONTROL STUDY; GENETIC PREDISPOSITION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; INTESTINE; METABOLISM; MICROARRAY ANALYSIS; SEQUENCE ANALYSIS; STATISTICAL MODEL;

CASE-CONTROL STUDIES; CROHN DISEASE; GENE EXPRESSION; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INTERFERON-GAMMA; INTESTINES; LINKAGE DISEQUILIBRIUM; LOGISTIC MODELS; MACROPHAGES; MICROARRAY ANALYSIS; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; SEQUENCE ANALYSIS, RNA;

EID: 84936766731     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv142     Document Type: Article

References (48)

1. Jostins, L., Ripke, S., Weersma, R.K., Duerr, R.H., McGovern, D.P., Hui, K.Y., Lee, J.C., Schumm, L.P., Sharma, Y., Anderson, C.A. et al. (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491, 119-124.
2. Nicolae, D.L., Gamazon, E., Zhang, W., Duan, S., Dolan, M.E. and Cox, N.J. (2010) Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. PLoS Genet., 6, e1000888.
3. He, X., Fuller, C.K., Song, Y., Meng, Q., Zhang, B., Yang, X. and Li, H. (2013) Sherlock: detecting gene-disease associations by matching patterns of expression QTL and GWAS. Am. J. Hum. Genet., 92, 667-680.
4. Nica, A.C., Parts, L., Glass, D., Nisbet, J., Barrett, A., Sekowska, M., Travers, M., Potter, S., Grundberg, E., Small, K. et al. (2011) The architecture of gene regulatory variation across multiple human tissues: the MuTHER study. PLoS Genet., 7, e1002003.
5. Fu, J., Wolfs, M.G., Deelen, P., Westra, H.J., Fehrmann, R.S., Te Meerman, G.J., Buurman, W.A., Rensen, S.S., Groen, H.J., Weersma, R.K. et al. (2012) Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression. PLoS Genet., 8, e1002431.
6. Fairfax, B.P., Humburg, P., Makino, S., Naranbhai, V., Wong, D., Lau, E., Jostins, L., Plant, K., Andrews, R., McGee, C. et al. (2014) Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science, 343, 1246949.
7. Duerr, R.H., Taylor, K.D., Brant, S.R., Rioux, J.D., Silverberg, M.S., Daly, M.J., Steinhart, A.H., Abraham, C., Regueiro, M., Griffiths, A. et al. (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science, 314, 1461-1463.
8. Cargill, M., Schrodi, S.J., Chang, M., Garcia, V.E., Brandon, R., Callis, K.P., Matsunami, N., Ardlie, K.G., Civello, D., Catanese, J.J. et al. (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet., 80, 273-290.
9. Australo-Anglo-American Spondyloarthritis, C., Reveille, J.D., Sims, A.M., Danoy, P., Evans, D.M., Leo, P., Pointon, J.J., Jin, R., Zhou, X., Bradbury, L.A. et al. (2010) Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat. Genet., 42, 123-127.
10. Wellcome Trust Case Control, C., Australo-Anglo-American Spondylitis, C., Burton, P.R., Clayton, D.G., Cardon, L.R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D.P., McCarthy, M.I. et al. (2007) Association scan of 14, 500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet., 39, 1329-1337.
11. Weaver, C.T. and Hatton, R.D. (2009) Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective. Nat. Rev. Immunol., 9, 883-889.
12. Spits, H., Artis, D., Colonna, M., Diefenbach, A., Di Santo, J.P., Eberl, G., Koyasu, S., Locksley, R.M., McKenzie, A.N., Mebius, R.E. et al. (2013) Innate lymphoid cells-a proposal for uniform nomenclature. Nat. Rev. Immunol., 13, 145-149.
13. Cotsapas, C., Voight, B.F., Rossin, E., Lage, K., Neale, B.M., Wallace, C., Abecasis, G.R., Barrett, J.C., Behrens, T., Cho, J. et al. (2011) Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet., 7, e1002254.
14. Liu, J.Z., McRae, A.F., Nyholt, D.R., Medland, S.E., Wray, N.R., Brown, K.M., Investigators, A., Hayward, N.K., Montgomery, G. W., Visscher, P.M. et al. (2010)Aversatile gene-based test for genome-wide association studies. Am. J. Hum. Genet., 87, 139-145.
15. Zhang, W., Ferguson, J., Ng, S.M., Hui, K., Goh, G., Lin, A., Esplugues, E., Flavell, R.A., Abraham, C., Zhao, H. et al. (2012) Effector CD4+ T cell expression signatures and immunemediated disease associated genes. PloS One, 7, e38510.
16. Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.C. and Muller, M. (2011) pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics, 12, 77.
17. Eden, E., Navon, R., Steinfeld, I., Lipson, D. and Yakhini, Z. (2009) GOrilla: a tool for discovery and visualization of enrichedGOterms in ranked gene lists. BMC Bioinformatics, 10, 48.
18. Pena, O.M., Pistolic, J., Raj, D., Fjell, C.D. and Hancock, R.E. (2011) Endotoxin tolerance represents a distinctive state of alternative polarization (M2) in human mononuclear cells. J. Immunol., 186, 7243-7254.
19. Uhlig, H.H. (2013) Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease. Gut, 62, 1795-1805.
20. Ogura, Y., Bonen, D.K., Inohara, N., Nicolae, D.L., Chen, F.F., Ramos, R., Britton, H., Moran, T., Karaliuskas, R., Duerr, R.H. et al. (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature, 411, 603-606.
21. Murthy, A., Li, Y., Peng, I., Reichelt, M., Katakam, A.K., Noubade, R., Roose-Girma, M., DeVoss, J., Diehl, L., Graham, R.R. et al. (2014) A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Nature, 506, 456-462.
22. Glocker, E.O., Frede, N., Perro, M., Sebire, N., Elawad, M., Shah, N. and Grimbacher, B. (2010) Infant colitis-it's in the genes. Lancet, 376, 1272.
23. Glocker, E.O., Kotlarz, D., Boztug, K., Gertz, E.M., Schaffer, A.A., Noyan, F., Perro, M., Diestelhorst, J., Allroth, A., Murugan, D. et al. (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med., 361, 2033-2045.
24. Pigneur, B., Escher, J., Elawad, M., Lima, R., Buderus, S., Kierkus, J., Guariso, G., Canioni, D., Lambot, K., Talbotec, C. et al. (2013) Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group. Inflamm. Bowel Dis., 19, 2820-2828.
25. Zeissig, Y., Petersen, B.S., Milutinovic, S., Bosse, E., Mayr, G., Peuker, K., Hartwig, J., Keller, A., Kohl, M., Laass, M.W. et al. (2014) XIAP variants in male Crohn's disease. Gut, 64, 66-76.
26. Rivas, M.A., Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C.K., Boucher, G., Ripke, S., Ellinghaus, D., Burtt, N. et al. (2011) Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat. Genet., 43, 1066-1073.
27. Raychaudhuri, S., Plenge, R.M., Rossin, E.J., Ng, A.C., International Schizophrenia, C., Purcell, S.M., Sklar, P., Scolnick, E.M., Xavier, R.J., Altshuler, D. et al. (2009) Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet., 5, e1000534.
28. Rossin, E.J., Lage, K., Raychaudhuri, S., Xavier, R.J., Tatar, D., Benita, Y., International Inflammatory Bowel Disease Genetics, C., Cotsapas, C. and Daly, M.J. (2011) Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet., 7, e1001273.
29. Farh, K.K., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W.J., Beik, S., Shoresh, N., Whitton, H., Ryan, R.J., Shishkin, A.A. et al. (2015) Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature, 518, 337-343.
30. Abraham, C. and Cho, J.H. (2009) Inflammatory bowel disease. N. Engl. J. Med., 361, 2066-2078.
31. Rioux, J.D., Daly, M.J., Silverberg, M.S., Lindblad, K., Steinhart, H., Cohen, Z., Delmonte, T., Kocher, K., Miller, K., Guschwan, S. et al. (2001) Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat. Genet., 29, 223-228.
32. Illumina (2011) Illumina Human BodyMap Project. Available from: http://www.ebi.ac.uk/arrayexpress (query ID: EMTAB-513).
33. Sipos, F., Galamb, O., Wichmann, B., Krenacs, T., Toth, K., Leiszter, K., Muzes, G., Zagoni, T., Tulassay, Z. and Molnar, B. (2011) Peripheral blood based discrimination of ulcerative colitis and Crohn's disease from non-IBD colitis by genome-wide gene expression profiling. Dis. Markers, 30, 1-17.
34. Trapnell, C., Roberts, A., Goff, L., Pertea, G., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S.L., Rinn, J.L. and Pachter, L. (2012) Differential gene and transcript expression analysis of RNAseq experiments with TopHat and Cufflinks. Nat. Protoc., 7, 562-578.
35. Trapnell, C., Pachter, L. and Salzberg, S.L. (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics (Oxford, England), 25, 1105-1111.
36. Anders, S. and Huber, W. (2010) Differential expression analysis for sequence count data. Genome Biol., 11, R106.
37. Franke, A., McGovern, D.P., Barrett, J.C., Wang, K., Radford-Smith, G.L., Ahmad, T., Lees, C.W., Balschun, T., Lee, J., Roberts, R. et al. (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet., 42, 1118-1125.
38. Devlin, B. and Roeder, K. (1999) Genomic control for association studies. Biometrics, 55, 997-1004.
39. Gaffney, D.J., Veyrieras, J.B., Degner, J.F., Pique-Regi, R., Pai, A. A., Crawford, G.E., Stephens, M., Gilad, Y. and Pritchard, J.K. (2012) Dissecting the regulatory architecture of gene expression QTLs. Genome Biol., 13, R7.
40. Dixon, A.L., Liang, L., Moffatt, M.F., Chen, W., Heath, S., Wong, K.C., Taylor, J., Burnett, E., Gut, I., Farrall, M. et al. (2007) A genome-wide association study of global gene expression. Nat. Genet., 39, 1202-1207.
41. Greenawalt, D.M., Dobrin, R., Chudin, E., Hatoum, I.J., Suver, C., Beaulaurier, J., Zhang, B., Castro, V., Zhu, J., Sieberts, S.K. et al. (2011) A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort. Genome Res., 21, 1008-1016.
42. Kabakchiev, B. and Silverberg, M.S. (2013) Expression quantitative trait loci analysis identifies associations between genotype and gene expression in human intestine. Gastroenterology, 144, 1488-1496, 1496.e1-3.
43. Hindorff, L.A., Morales, M.J., Morales, J., Junkins, H.A., Hall, P.N., Klemm, A.K. and Manolio, T.A. A Catalog of Published Genome-Wide Association Studies. Available from: www. genome.gov/gwastudies. Accessed in 2013.
44. Rosenbloom, K.R., Sloan, C.A., Malladi, V.S., Dreszer, T.R., Learned, K., Kirkup, V.M., Wong, M.C., Maddren, M., Fang, R., Heitner, S.G. et al. (2013) ENCODE data in the UCSC Genome Browser: year 5 update. Nucleic Acids Res., 41, D56-D63.
45. R_Core_Team. (2014) R: A Language and Environment for Statistical computing. Available from: http://www. R-project.org.
46. Du, P., Kibbe, W.A. and Lin, S.M. (2008) lumi: a pipeline for processing Illumina microarray. Bioinformatics, 24, 1547-1548.
47. Gentleman, R.C., Carey, V.J., Bates, D.M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J. et al. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol., 5, R80.
48. Warnes, G.R., Bolker, B., Bonebakker, L., Gentleman, R., Liaw, W.H.A., Lumley, T., Maechler, M., Magnusson, A., Moeller, S., Schwartz, M., Venables, B. (2014) gplots: Various R Programming Tools for Plotting Data. Available from: http://CRAN. Rproject. org/package=gplots.