Integrating autoimmune risk loci with gene-expression data identifies specific pathogenic immune cell subsets

American Journal of Human Genetics

Volumn 89, Issue 4, 2011, Pages 496-506

  Hu, Xinli ^a,b,c   Kim, Hyun ^a   Stahl, Eli ^a,b   Plenge, Robert ^a,b   Daly, Mark ^b,d   Raychaudhuri, Soumya ^a,b,e  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c HARVARD UNIVERSITY   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

^e LABORATORY FOR MOLECULAR MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; ANIMAL CELL; ARTICLE; AUTOIMMUNE DISEASE; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL FUNCTION; CELL TYPE; GENE EXPRESSION PROFILING; GENE LOCUS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; IMMUNOCOMPETENT CELL; NONHUMAN; PATHOGENICITY; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS;

ALLELES; ANIMALS; ARTHRITIS, RHEUMATOID; AUTOIMMUNE DISEASES; CD4-POSITIVE T-LYMPHOCYTES; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; IMMUNE SYSTEM; MICE; MODELS, STATISTICAL; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK;

MURINAE;

EID: 80053896562     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2011.09.002     Document Type: Article

References (54)

1. J.C. Barrett, D.G. Clayton, P. Concannon, B. Akolkar, J.D. Cooper, H.A. Erlich, C. Julier, G. Morahan, J. Nerup, C. Nierras Type 1 Diabetes Genetics Consortium Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes Nat. Genet. 41 2009 703 707
2. S. Raychaudhuri Recent advances in the genetics of rheumatoid arthritis Curr. Opin. Rheumatol. 22 2010 109 118
3. A. Franke, D.P. McGovern, J.C. Barrett, K. Wang, G.L. Radford-Smith, T. Ahmad, C.W. Lees, T. Balschun, J. Lee, and R. Roberts Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci Nat. Genet. 42 2010 1118 1125
4. S.M. Purcell, N.R. Wray, J.L. Stone, P.M. Visscher, M.C. O'Donovan, P.F. Sullivan, P. Sklar International Schizophrenia Consortium Common polygenic variation contributes to risk of schizophrenia and bipolar disorder Nature 460 2009 748 752
5. L.A. Hindorff, P. Sethupathy, H.A. Junkins, E.M. Ramos, J.P. Mehta, F.S. Collins, and T.A. Manolio Potential etiologic and functional implications of genome-wide association loci for human diseases and traits Proc. Natl. Acad. Sci. USA 106 2009 9362 9367
6. H. Zhong, J. Beaulaurier, P.Y. Lum, C. Molony, X. Yang, D.J. Macneil, D.T. Weingarth, B. Zhang, D. Greenawalt, and R. Dobrin Liver and adipose expression associated SNPs are enriched for association to type 2 diabetes PLoS Genet. 6 2010 e1000932
7. A.S. Dimas, S. Deutsch, B.E. Stranger, S.B. Montgomery, C. Borel, H. Attar-Cohen, C. Ingle, C. Beazley, M. Gutierrez Arcelus, and M. Sekowska Common regulatory variation impacts gene expression in a cell type-dependent manner Science 325 2009 1246 1250
8. A.L. Price, A. Helgason, G. Thorleifsson, S.A. McCarroll, A. Kong, and K. Stefansson Single-tissue and cross-tissue heritability of gene expression via identity-by-descent in related or unrelated individuals PLoS Genet. 7 2011 e1001317
9. J. Ernst, P. Kheradpour, T.S. Mikkelsen, N. Shoresh, L.D. Ward, C.B. Epstein, X. Zhang, L. Wang, R. Issner, and M. Coyne Mapping and analysis of chromatin state dynamics in nine human cell types Nature 473 2011 43 49
10. N.D. Heintzman, G.C. Hon, R.D. Hawkins, P. Kheradpour, A. Stark, L.F. Harp, Z. Ye, L.K. Lee, R.K. Stuart, and C.W. Ching Histone modifications at human enhancers reflect global cell-type-specific gene expression Nature 459 2009 108 112
11. G.S. Firestein Evolving concepts of rheumatoid arthritis Nature 423 2003 356 361 (Pubitemid 40852711)
12. B.T. Wipke, and P.M. Allen Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis J. Immunol. 167 2001 1601 1608 (Pubitemid 32703161)
13. D.M. Lee, D.S. Friend, M.F. Gurish, C. Benoist, D. Mathis, and M.B. Brenner Mast cells: A cellular link between autoantibodies and inflammatory arthritis Science 297 2002 1689 1692 (Pubitemid 35000781)
14. R.W. Kinne, R. Bräuer, B. Stuhlmüller, E. Palombo-Kinne, and G.R. Burmester Macrophages in rheumatoid arthritis Arthritis Res. 2 2000 189 202 (Pubitemid 32223726)
15. E. Boilard, P.A. Nigrovic, K. Larabee, G.F. Watts, J.S. Coblyn, M.E. Weinblatt, E.M. Massarotti, E. Remold-O'Donnell, R.W. Farndale, and J. Ware Platelets amplify inflammation in arthritis via collagen-dependent microparticle production Science 327 2010 580 583
16. T. Pap, U. Müller-Ladner, R.E. Gay, and S. Gay Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis Arthritis Res. 2 2000 361 367 (Pubitemid 32223765)
17. S. Lefvre, A. Knedla, C. Tennie, A. Kampmann, C. Wunrau, R. Dinser, A. Korb, E.M. Schnäker, I.H. Tarner, and P.D. Robbins Synovial fibroblasts spread rheumatoid arthritis to unaffected joints Nat. Med. 15 2009 1414 1420
18. S.A. McCarroll, A. Huett, P. Kuballa, S.D. Chilewski, A. Landry, P. Goyette, M.C. Zody, J.L. Hall, S.R. Brant, and J.H. Cho Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease Nat. Genet. 40 2008 1107 1112
19. C.A. Dendrou, V. Plagnol, E. Fung, J.H. Yang, K. Downes, J.D. Cooper, S. Nutland, G. Coleman, M. Himsworth, and M. Hardy Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource Nat. Genet. 41 2009 1011 1015
20. A.A. Alizadeh, M.B. Eisen, R.E. Davis, C. Ma, I.S. Lossos, A. Rosenwald, J.C. Boldrick, H. Sabet, T. Tran, and X. Yu Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling Nature 403 2000 503 511 (Pubitemid 30082188)
21. T.R. Golub, D.K. Slonim, P. Tamayo, C. Huard, M. Gaasenbeek, J.P. Mesirov, H. Coller, M.L. Loh, J.R. Downing, and M.A. Caligiuri Molecular classification of cancer: class discovery and class prediction by gene expression monitoring Science 286 1999 531 537
22. G. Hyatt, R. Melamed, R. Park, R. Seguritan, C. Laplace, L. Poirot, S. Zucchelli, R. Obst, M. Matos, and E. Venanzi Gene expression microarrays: glimpses of the immunological genome Nat. Immunol. 7 2006 686 691 (Pubitemid 43905863)
23. S. Raychaudhuri, J.M. Korn, S.A. McCarroll, D. Altshuler, P. Sklar, S. Purcell, M.J. Daly International Schizophrenia Consortium Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function PLoS Genet. 6 2010 e1001097
24. R.A. Irizarry, B. Hobbs, F. Collin, Y.D. Beazer-Barclay, K.J. Antonellis, U. Scherf, and T.P. Speed Exploration, normalization, and summaries of high density oligonucleotide array probe level data Biostatistics 4 2003 249 264
25. S. Raychaudhuri, R.M. Plenge, E.J. Rossin, A.C.Y. Ng, S.M. Purcell, P. Sklar, E.M. Scolnick, R.J. Xavier, D. Altshuler, M.J. Daly International Schizophrenia Consortium Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions PLoS Genet. 5 2009 e1000534
26. E.J. Rossin, K. Lage, S. Raychaudhuri, R.J. Xavier, D. Tatar, Y. Benita, C. Cotsapas, M.J. Daly International Inflammatory Bowel Disease Genetics Constortium Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology PLoS Genet. 7 2011 e1001273
27. A.I. Su, T. Wiltshire, S. Batalov, H. Lapp, K.A. Ching, D. Block, J. Zhang, R. Soden, M. Hayakawa, and G. Kreiman A gene atlas of the mouse and human protein-encoding transcriptomes Proc. Natl. Acad. Sci. USA 101 2004 6062 6067 (Pubitemid 38520528)
28. S. Myers, L. Bottolo, C. Freeman, G. McVean, and P. Donnelly A fine-scale map of recombination rates and hotspots across the human genome Science 310 2005 321 324 (Pubitemid 41457199)
29. H. Lango Allen, K. Estrada, G. Lettre, S.I. Berndt, M.N. Weedon, F. Rivadeneira, C.J. Willer, A.U. Jackson, S. Vedantam, and S. Raychaudhuri Hundreds of variants clustered in genomic loci and biological pathways affect human height Nature 467 2010 832 838
30. T.M. Teslovich, K. Musunuru, A.V. Smith, A.C. Edmondson, I.M. Stylianou, M. Koseki, J.P. Pirruccello, S. Ripatti, D.I. Chasman, and C.J. Willer Biological, clinical and population relevance of 95 loci for blood lipids Nature 466 2010 707 713
31. L. Stryer Biochemistry 2000 W.H. Freeman New York
32. H.H. Hobbs, M.S. Brown, and J.L. Goldstein Molecular genetics of the LDL receptor gene in familial hypercholesterolemia Hum. Mutat. 1 1992 445 466
33. K. Musunuru, A. Strong, M. Frank-Kamenetsky, N.E. Lee, T. Ahfeldt, K.V. Sachs, X. Li, H. Li, N. Kuperwasser, and V.M. Ruda From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus Nature 466 2010 714 719
34. E.K. Speliotes, C.J. Willer, S.I. Berndt, K.L. Monda, G. Thorleifsson, A.U. Jackson, H.L. Allen, C.M. Lindgren, J. Luan, and R. Magi Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index Nat. Genet. 42 2010 937 948
35. K. Clément, C. Vaisse, N. Lahlou, S. Cabrol, V. Pelloux, D. Cassuto, M. Gourmelen, C. Dina, J. Chambaz, and J.M. Lacorte A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction Nature 392 1998 398 401 (Pubitemid 28168737)
36. J. Pinkney, J. Wilding, G. Williams, and I. MacFarlane Hypothalamic obesity in humans: what do we know and what can be done? Obes. Rev. 3 2002 27 34 (Pubitemid 34827143)
37. C.J. Willer, E.K. Speliotes, R.J. Loos, S. Li, C.M. Lindgren, I.M. Heid, S.I. Berndt, A.L. Elliott, A.U. Jackson, C. Lamina Wellcome Trust Case Control Consortium Genetic Investigation of ANthropometric Traits Consortium Six new loci associated with body mass index highlight a neuronal influence on body weight regulation Nat. Genet. 41 2009 25 34
38. S. Raychaudhuri, J.M. Stuart, and R.B. Altman Principal components analysis to summarize microarray experiments: application to sporulation time series Pac. Symp. Biocomput. 2000 2000 455 466
39. V. Gateva, J.K. Sandling, G. Hom, K.E. Taylor, S.A. Chung, X. Sun, W. Ortmann, R. Kosoy, R.C. Ferreira, and G. Nordmark A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus Nat. Genet. 41 2009 1228 1233
40. J.W. Han, H.F. Zheng, Y. Cui, L.D. Sun, D.Q. Ye, Z. Hu, J.H. Xu, Z.M. Cai, W. Huang, and G.P. Zhao Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus Nat. Genet. 41 2009 1234 1237
41. J.B. Harley, M.E. Alarcón-Riquelme, L.A. Criswell, C.O. Jacob, R.P. Kimberly, K.L. Moser, B.P. Tsao, T.J. Vyse, C.D. Langefeld, S.K. Nath International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN) Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci Nat. Genet. 40 2008 204 210 (Pubitemid 351171405)
42. G. Hom, R.R. Graham, B. Modrek, K.E. Taylor, W. Ortmann, S. Garnier, A.T. Lee, S.A. Chung, R.C. Ferreira, and P.V. Pant Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX N. Engl. J. Med. 358 2008 900 909 (Pubitemid 351397089)
43. S.V. Kozyrev, A.K. Abelson, J. Wojcik, A. Zaghlool, M.V. Linga Reddy, E. Sanchez, I. Gunnarsson, E. Svenungsson, G. Sturfelt, and A. Jönsen Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus Nat. Genet. 40 2008 211 216 (Pubitemid 351171404)
44. E.A. Stahl, S. Raychaudhuri, E.F. Remmers, G. Xie, S. Eyre, B.P. Thomson, Y. Li, F.A. Kurreeman, A. Zhernakova, A. Hinks BIRAC Consortium YEAR Consortium Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci Nat. Genet. 42 2010 508 514
45. A. Zhernakova, E.A. Stahl, G. Trynka, S. Raychaudhuri, E.A. Festen, L. Franke, H.J. Westra, R.S. Fehrmann, F.A. Kurreeman, and B. Thomson Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci PLoS Genet. 7 2011 e1002004
46. O.T. Chan, M.P. Madaio, and M.J. Shlomchik The central and multiple roles of B cells in lupus pathogenesis Immunol. Rev. 169 1999 107 121 (Pubitemid 29338727)
47. S.V. Navarra, R.M. Guzmán, A.E. Gallacher, S. Hall, R.A. Levy, R.E. Jimenez, E.K. Li, M. Thomas, H.Y. Kim, M.G. León BLISS-52 Study Group Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial Lancet 377 2011 721 731
48. Y. Zheng, H. Liu, J. Coughlin, J. Zheng, L. Li, and J.C. Stone Phosphorylation of RasGRP3 on threonine 133 provides a mechanistic link between PKC and Ras signaling systems in B cells Blood 105 2005 3648 3654 (Pubitemid 40628212)
49. J.H. Cho The genetics and immunopathogenesis of inflammatory bowel disease Nat. Rev. Immunol. 8 2008 458 466 (Pubitemid 351733422)
50. D.C. Baumgart, and S.R. Carding Inflammatory bowel disease: cause and immunobiology Lancet 369 2007 1627 1640 (Pubitemid 46722636)
51. R. Cooney, J. Baker, O. Brain, B. Danis, T. Pichulik, P. Allan, D.J. Ferguson, B.J. Campbell, D. Jewell, and A. Simmons NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation Nat. Med. 16 2010 90 97
52. M.A. Travis, B. Reizis, A.C. Melton, E. Masteller, Q. Tang, J.M. Proctor, Y. Wang, X. Bernstein, X. Huang, and L.F. Reichardt Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice Nature 449 2007 361 365 (Pubitemid 47443473)
53. L. Franke, H. van Bakel, L. Fokkens, E.D. de Jong, M. Egmont-Petersen, and C. Wijmenga Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes Am. J. Hum. Genet. 78 2006 1011 1025 (Pubitemid 43787692)
54. R. Chen, A.A. Morgan, J. Dudley, T. Deshpande, L. Li, K. Kodama, A.P. Chiang, and A.J. Butte FitSNPs: highly differentially expressed genes are more likely to have variants associated with disease Genome Biol. 9 2008 R170