Mapping of immune-mediated disease genes

Annual Review of Genomics and Human Genetics

Volumn 14, Issue , 2013, Pages 325-353

  Ricaño Ponce, Isis ^a   Wijmenga, Cisca ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Autoimmunity; EQTL; Genome wide association study; Immunogenetics; Noncoding

Indexed keywords

CASPASE RECRUITMENT DOMAIN PROTEIN 15; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HLA B27 ANTIGEN; HLA C ANTIGEN; INTERLEUKIN 2; INTERLEUKIN 21; INTERLEUKIN 23 RECEPTOR; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE 3; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; PROTEIN KINASE TYK2; STAT1 PROTEIN; STAT2 PROTEIN; STAT3 PROTEIN; STAT4 PROTEIN; STAT5A PROTEIN; STAT5B PROTEIN; STAT6 PROTEIN; TUMOR NECROSIS FACTOR RECEPTOR 1;

ANKYLOSING SPONDYLITIS; CELIAC DISEASE; CHROMOSOME 16; CROHN DISEASE; DISEASE COURSE; GENE CONTROL; GENE EXPRESSION; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE MAPPING; GENE MUTATION; GENETIC ASSOCIATION; GENETIC PREDISPOSITION; GENETIC VARIABILITY; GENOME IMPRINTING; GENOTYPE ENVIRONMENT INTERACTION; GRAVES DISEASE; HASHIMOTO DISEASE; HERITABILITY; HETEROZYGOTE; HISTONE MODIFICATION; HOMOZYGOTE; HUMAN; IMMUNE MEDIATED DISEASE; IMMUNOGLOBULIN A DEFICIENCY; IMMUNOPATHOLOGY; INSULIN DEPENDENT DIABETES MELLITUS; MULTIPLE SCLEROSIS; NONHUMAN; PREVALENCE; PRIMARY BILIARY CIRRHOSIS; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; SEX RATIO; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS; TH17 CELL; ULCERATIVE COLITIS; X CHROMOSOME INACTIVATION;

ANIMALS; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; IMMUNE SYSTEM DISEASES; INFLAMMATION; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84884330381     PISSN: 15278204     EISSN: 1545293X     Source Type: Book Series    
DOI: 10.1146/annurev-genom-091212-153450     Document Type: Review

References (125)

1. -1000 Genomes Proj. Consort. 2010. A map of human genome variation from population-scale sequencing. Nature 467:1061-73
2. Abi-Rached L, JobinM J, Kulkarni S, McWhinnie A, Dalva K, et al. 2011. The shaping of modern human immune systems by multiregional admixture with archaic humans. Science 334:89-94
3. Adrianto I, Wen F, Templeton A, Wiley G, King JB, et al. 2011. Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat. Genet. 43:253-58
4. Amur S, Parekh A, Mummaneni P. 2012. Sex differences and genomics in autoimmune diseases. J. Autoimmun. 38:J254-65
5. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, et al. 2011. Meta-Analysis identifies 29 additional ulcerative colitis risk loc i, increasing the number of confirmed associations to 47. Nat. Genet. 43:246-52
6. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, et al. 2011. Enterotypes of the human gut microbiome. Nature 473:174-80
7. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, et al. 2009. Genome-wide association study and meta-Analysis find that over 40 loci affect risk of type 1 diabetes. Nat. Genet. 41:703-7
8. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, et al. 2008. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat. Genet. 40:955-62
9. Becker KG, White SL, Muller J, Engel J. 2000. BBID: The biological biochemical image database. Bioinformatics 16:745-46
10. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, et al. 2004. Amissense singlenucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am. J. Hum. Genet. 75:330-37
11. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, et al. 2004. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat. Genet. 36:337-38
12. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, et al. 2007. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 39:1329-37
13. Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, et al. 2007. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661-78
14. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, et al. 2008. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456:259-63
15. Cadwell K, Patel KK, Maloney NS, Liu T-C, Ng AC Y, et al. 2010. Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141:1135-45
16. Candore G, Lio D, Colonna Romano G, Caruso C. 2002. Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: Effect of multiple gene interactions. Autoimmun. Rev. 1:29-35
17. Chang JT, Nevins JR. 2006. GATHER: A systems approach to interpreting genomic signatures. Bioinformatics 22:2926-33
18. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, et al. 2007. Replicating genotypephenotype associations. Nature 447:655-60
19. Chao MJ, Herrera BM, Ramagopalan SV, Deluca G, Handunetthi L, et al. 2010. Parent-of-origin effects at the major histocompatibility complex in multiple sclerosis. Hum. Mol. Genet. 19:3679-89
20. Chu X, Pan C-M, Zhao S-X, Liang J, Gao G-Q, et al. 2011. A genome-wide association study identifies two new risk loci for Graves' disease. Nat. Genet. 43:897-901
21. Cooney R, Baker J, Brain O, Danis B, Pichulik T, et al. 2010. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16:90-97
22. Cooper GS, Bynum ML K, Somers EC. 2009. Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases. J. Autoimmun. 33:197-207
23. Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, et al. 2011. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 7:e1002254
24. Cuthbert AP, Fisher SA, Mirza MM, King K, Hampe J, et al. 2002. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology 122:867-74
25. De Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D. 2005. Efficiency and power in genetic association studies. Nat. Genet. 37:1217-23
26. Di Cagno R, De Angelis M, De Pasquale I, Ndagijimana M, Vernocchi P, et al. 2011. Duodenal and faecal microbiota of celiac children: Molecula r, phenotype and metabolome characterization. BMC Microbiol. 11:219
27. Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB. 2010. Rare variants create synthetic genome-wide associations. PLoS Biol. 8:e1000294
28. Dubois PC A, Trynka G, Franke L, Hunt KA, Romanos J, et al. 2010. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42:295-302
29. ENCODE Proj. Consort. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 488:57-74
30. Evans DM, Spencer CC A, Pointon JJ, Su Z, Harvey D, et al. 2011. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat. Genet. 43:761-67
31. Eyre S, Bowes J, Diogo D, Lee A, Barton A, et al. 2012. High-Density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat. Genet. 44:1336-40
32. Fehrmann RS N, Jansen RC, Veldink JH, Westra HJ, Arends D, et al. 2011. Trans-eQTLs reveal that independent genetic variants associated with a complex phenotype converge on intermediate gene s, with a major role for the HLA. PLoS Genet. 7:e1002197
33. Fernando MM, Stevens CR, Walsh EC, De Jager PL, Goyette P, et al. 2008. Defining the role of the MHC in autoimmunity: A review and pooled analysis. PLoS Genet. 4:e1000024
34. Festen EA M, Goyette P, Green T, Boucher G, Beauchamp C, et al. 2011. A meta-Analysis of genomewide association scans identifies IL18RA P, PTPN2, TAGA P, and PUS10 as shared risk loci for Crohn's disease and celiac disease. PLoS Genet. 7:e1001283
35. Franke A, McGovern DP B, Barrett JC, Wang K, Radford-Smith GL, et al. 2010. Genome-wide metaanalysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 42:1118-25
36. Franke L, vanBakel H, Fokkens L, De Jong ED, Egmont-Petersen M, Wijmenga C. 2006. Reconstruction of a functional human gene networ k, with an application for prioritizing positional candidate genes. Am. J. Hum. Genet. 78:1011-25
37. Fu J, Festen EA M, Wijmenga C. 2011. Multi-ethnic studies in complex traits. Hum. Mol. Genet. 20:R206-13
38. Fu J, Wolfs MG M, Deelen P, Westra HJ, Fehrmann RS N, et al. 2012. Unraveling the regulatory mechanisms underlying tissue-Dependent genetic variation of gene expression. PLoS Genet. 8:e1002431
39. Galanter JM, Fernandez-Lopez JC, Gignoux CR, Barnholtz-Sloan J, Fernandez-Rozadilla C, et al. 2012. Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas. PLoS Genet. 8:e1002554
40. Gamazon ER, Ziliak D, Im HK, LaCroix B, Park DS, et al. 2012. Genetic architecture of microRNA expression: Implications for the transcriptome and complex traits. Am. J. Hum. Genet. 90:1046-63
41. Gibson G. 2012. Rare and common variants: Twenty arguments. Nat. Rev. Genet. 13:135-45
42. Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, et al. 2002. The first large population based twin study of coeliac disease. Gut 50:624-28
43. Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, et al. 2012. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 488:508-11
44. Hindorff LA, MacArthur J, Morales J, Junkins HA, Hall PN, et al. 2013. A catalog of published genome-wide association studies. Natl. Hum. Genome Res. Inst. Div. Genomic Med., Bethesd a, MD. http://www.genome.gov/gwastudies
45. Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, et al. 2004. Gene map of the extended human MHC. Nat. Rev. Genet. 5:889-99
46. Hu X, Kim H, Stahl E, Plenge R, Daly M, Raychaudhuri S. 2011. Integrating autoimmune risk loci with gene-expression data identifies specific pathogenic immune cell subsets. Am. J. Hum. Genet. 89:496-506
47. Huang DW, Sherman BT, Lempicki RA. 2009. Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1-13
48. Huang DW, Sherman BT, Lempicki RA. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4:44-57
49. Huang J, Ellinghaus D, Franke A, Howie B, Li Y. 2012. 1000 Genomes-based imputation identifies novel and refined associations for the Wellcome Trust Case Control Consortium phase 1 data. Eur. J. Hum. Genet. 20:801-5
50. Hughes A. 2007. Natural selection and sequence polymorphism. Vide o, 34 mi n, from Human Population Genetics: Evolution and Variatio n, Biomedical and Life Sciences Collectio n, ed. LL Cavalli-Sforz a, M Feldman. London: Henry Stewart Talks. http://hstalks.com/main/ view-talk.php?t=312&r=27&j= 757&c=252
51. Hughes T, Adler A, Kelly JA, Kaufman KM, Williams AH, et al. 2012. Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus. Arthritis Rheum. 64:485-92
52. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, et al. 2001. Association ofNOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411:599-603
53. Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, et al. 1996. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature 379:821-23
54. Hunt KA, Smyth DJ, Balschun T, Ban M, Mistry V, et al. 2012. Rare and functional SIAE variants are not associated with autoimmune disease risk in up to 66,924 individuals of European ancestry. Nat. Genet. 44:3-5
55. Int. HapMap Consort. 2005. A haplotype map of the human genome. Nature 437:1299-320
56. Int. Mult. Scler. Genet. Consort. (IMSGC). 2010. Evidence for polygenic susceptibility to multiple sclerosis-The shape of things to come. Am. J. Hum. Genet. 86:621-25
57. Jacobson EM, Huber A, Tomer Y. 2008. The HLA gene complex in thyroid autoimmunity: From epidemiology to etiology. J. Autoimmun. 30:58-62
58. Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O'Donnell CJ, De Bakker PIW. 2008. SNAP: A web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 24:2938-39
59. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, et al. 2012. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119-24
60. Kanehisa M, Goto S. 2000. KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Res. 28:27-30
61. Kanehisa M, Goto S, Sato Y, Furumichi M, TanabeM. 2012. KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 40:D109-14
62. Ke X. 2012. Presence of multiple independent effects in risk loci of common complex human diseases. Am. J. Hum. Genet. 91:185-92
63. Kenny EE, Pe'er I, Karban A, Ozelius L, Mitchell AA, et al. 2012. A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. PLoS Genet. 8:e1002559
64. Klitz W, Maiers M, Spellman S, Baxter-Lowe LA, Schmeckpeper B, et al. 2003. New HLA haplotype frequency reference standards: High-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans. Tissue Antigens 62:296-307
65. Kumar V, Westra HJ, Karjalainen J, Zhernakova DV, Esko T, et al. 2013. Human disease-Associated genetic variation impacts large intergenic non-coding RNA expression. PLoS Genet. 9:e1003201
66. Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, et al. 2004. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.Am. J. Hum. Genet. 75:504-7
67. Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, et al. 2012. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44:1341-48
68. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:860-921
69. Lee I, Blom UM, Wang PI, Shim JE, Marcotte EM. 2011. Prioritizing candidate disease genes by network-based boosting of genome-wide association data. Genome Res. 21:1109-21
70. Lio D, Candore G, Colombo A, Colonna Romano G, Gervasi F, et al. 2001.Agenetically determined high setting of TNF-Ainfluences immunologic parameters of HLA-B8,DR3 positive subjects: Implications for autoimmunity. Hum. Immunol. 62:705-13
71. Liu JZ, Almarri MA, Gaffney DJ, Mells GF, Jostins L, et al. 2012. Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 44:1137-41
72. Lleo A, Battezzati PM, Selmi C, Gershwin ME, Podda M. 2008. Is autoimmunity a matter of sex? Autoimmun. Rev. 7:626-30
73. Manjarrez-Ordu ño N, Marasco E, Chung SA, Katz MS, Kiridly JF, et al. 2012. CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation. Nat. Genet. 44:1227-30
74. Martin JE, Broen JC, Carmona FD, Teruel M, SimeonC P, et al. 2012. Identification of CSK as a systemic sclerosis genetic risk factor through genome wide association study follow-up. Hum. Mol. Genet. 21:2825-35
75. Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, et al. 2011. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat. Genet. 43:908-12
76. Maurano MT, Humbert R, Rynes E, Thurman RE, Haugen E, et al. 2012. Systematic localization of common disease-Associated variation in regulatory DNA. Science 337:1190-95
77. McGovern DP B, Jones MR, Taylor KD, Marciante K, Yan X, et al. 2010. Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Hum. Mol. Genet. 19:3468-76
78. Mells GF, Floyd JA B, Morley KI, Cordell HJ, Franklin CS, et al. 2011. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 43:329-32
79. Miao F, Smith DD, Zhang L, Min A, Feng W, Natarajan R. 2008. Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: An epigenetic study in diabetes. Diabetes 57:3189-98
80. Middleton D, Menchaca L, Rood H, Komerofsky R. 2003. New allele frequency database: Http://www.allelefrequencies.net. Tissue Antigens 61:403-7
81. Mitic T, Emanueli C. 2012. Diabetes-induced epigenetic signature in vascular cells. Endocr. Metab. Immune Disord. Drug Targets 12:107-17
82. Momozawa Y, Mni M, Nakamura K, Coppieters W, Almer S, et al. 2011. Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease. Nat. Genet. 43:43-47
83. Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, et al. 2010. The prevalence of celiac disease in Europe: Results of a centralize d, international mass screening project. Ann. Med. 42:587-95
84. Nejentsev S, Walker N, Riches D, Egholm M, Todd JA. 2009. Rare variants of IFIH1, a gene implicated in antiviral response s, protect against type 1 diabetes. Science 324:387-89
85. Nistico L, Buzzetti R, Pritchard LE, Van Der Auwera B, Giovannini C, et al. 1996. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated wit h, type 1 diabetes. Hum. Mol. Genet. 5:1075-80
86. Norton B, Pearson ES. 1976. A note on the background to, and refereeing of, R.A. Fisher's 1918 paper On the correlation between relatives on the supposition of Mendelian inheritance. Notes Rec. R. Soc. Lond. 31:151-62
87. O'shea JJ, Plenge R. 2012. JAK and STAT signaling molecules in immunoregulation and immunemediated disease. Immunity 36:542-50
88. Ozcelik T. 2008. X chromosome inactivation and female predisposition to autoimmunity. Clin. Rev. Allergy Immunol. 34:348-51
89. Patsopoulos NA, Esposito F, Reischl J, Lehr S, Bauer D, et al. 2011. Genome-wide meta-Analysis identifies novel multiple sclerosis susceptibility loci. Ann. Neurol. 70:897-912
90. Quintero-Ronderos P, Montoya-OrtizG. 2012. Epigenetics and autoimmune diseases. Autoimmune Dis. 2012:593720
91. Raelson JV, Little RD, Ruether A, Fournier H, Paquin B, et al. 2007. Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci. Proc. Natl. Acad. Sci. USA 104:14747-52
92. Raychaudhuri S, Plenge RM, Rossin EJ, Ng AC Y, Purcell SM, et al. 2009. Identifying relationships among genomic disease regions: Predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5:e1000534
93. Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, et al. 2009. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat. Genet. 41:1313-18
94. Risch N, MerikangasK. 1996. The future of genetic studies of complex human diseases. Science 273:1516-17
95. Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, et al. 2011. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat. Genet. 43:1066-73
96. Rosenberg NA, Huang L, Jewett EM, Szpiech ZA, Jankovic I, Boehnke M. 2010. Genome-wide association studies in diverse populations. Nat. Rev. Genet. 11:356-66
97. Rossin EJ, Lage K, Raychaudhuri S, Xavier RJ, Tatar D, et al. 2011. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet. 7:e1001273
98. Saulnier DM, Riehle K, Mistretta TA, Diaz MA, Mandal D, et al. 2011. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 141:1782-91
99. Sawcer S, Hellenthal G, Pirinen M, Spencer CC A, Patsopoulos NA, et al. 2011. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476:214-19
100. Schaub MA, Boyle AP, Kundaje A, Batzoglou S, Snyder M. 2012. Linking disease associations with regulatory information in the human genome. Genome Res. 22:1748-59
101. Shi JH, Zhou L, Zhernakova A, Qian JM, Zhu F, et al. 2011. Haplotype-based analysis of ulcerative colitis risk loci identifies both IL2 and IL21 as susceptibility genes in Han Chinese. Inflamm. Bowel Dis. 17:2472-79
102. Shriner D, Adeyemo A, Ramos E, Chen GJ, Rotimi CN. 2011. Mapping of disease-Associated variants in admixed populations. Genome Biol. 12:223
103. Shui JW, Larange A, Kim G, Vela JL, Zahner S, et al. 2012. HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria. Nature 488:222-25
104. Smyth D, Cooper JD, Collins JE, Heward JM, Franklyn JA, et al. 2004. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabete s, and evidence for its role as a general autoimmunity locus. Diabetes 53:3020-23
105. Stahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, et al. 2012. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat. Genet. 44:483-89
106. Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, et al. 2006. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: A longitudinal study. Am. J. Gastroenterol. 101:2333-40
107. Strange A, Capon F, Spencer CC A, Knight J, Weale ME, et al. 2010. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat. Genet. 42:985-90
108. Surolia I, Pirnie SP, Chellappa V, Taylor KN, Cariappa A, et al. 2010. Functionally defective germline variants of sialic acid acetylesterase in autoimmunity. Nature 466:243-47
109. Thomas PD, Kejariwal A, Campbell MJ, Mi H, Diemer K, et al. 2003. PANTHER: A browsable database of gene products organized by biological functio n, using curated protein family and subfamily classification. Nucleic Acids Res. 31:334-41
110. Trynka G, Hunt KA, Bockett NA, Romanos J, Mistry V, et al. 2011. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 43:1193-201
111. Twee-HeeOng R, Wang X, Liu X, Teo YY. 2012. Efficiency of trans-ethnic genome-wide meta-Analysis and fine-mapping. Eur. J. Hum. Genet. 20:1300-7
112. van Heel DA, Franke L, Hunt KA, Gwilliam R, Zhernakova A, et al. 2007. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat. Genet. 39:827-29
113. Velaga MR, Wilson V, Jennings CE, Owen CJ, Herington S, et al. 2004. The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves' disease. J. Clin. Endocrinol. Metab. 89:5862-65
114. Wallace C, Smyth DJ, Maisuria-Armer M, Walker NM, Todd JA, Clayton DG. 2009. The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nat. Genet. 42:68-71
115. Wandstrat A, Wakeland E. 2001. The genetics of complex autoimmune diseases: Non-MHC susceptibility genes. Nat. Immun. 2:802-9
116. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, et al. 2011. Selective IgA deficiency in autoimmune diseases. Mol. Med. 17:1383-96
117. Winkler CA, Nelson GW, Smith MW. 2010. Admixture mapping comes of age. Annu. Rev. Genomics Hum. Genet. 11:65-89
118. Yanagawa T, Hidaka Y, Guimaraes V, Soliman M, DeGroot LJ. 1995. CTLA-4 gene polymorphism associated with Graves' disease in a Caucasian population. J. Clin. Endocrinol. Metab. 80:41-45
119. Zheng J, Ibrahim S, Petersen F, Yu X. 2012. Meta-Analysis reveals an association of PTPN22 C1858T with autoimmune disease s, which depends on the localization of the affected tissue. Genes Immun. 13:641-52
120. Zhernakova A, Alizadeh BZ, Bevova M, van Leeuwen MA, Coenen MJ H, et al. 2007. Novel association in chromosome 4q27 region with rheumatoid arthritis and confirmation of type 1 diabetes point to a general risk locus for autoimmune diseases. Am. J. Hum. Genet. 81:1284-88
121. Zhernakova A, Eerligh P, Wijmenga C, Barrera P, Roep BO, KoelemanBP. 2005. Differential association of the PTPN22 coding variant with autoimmune diseases in aDutch population. Genes Immun. 6:459-61
122. Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, et al. 2011. Meta-Analysis of genomewide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 7:e1002004
123. Zhernakova A, Van Diemen CC, Wijmenga C. 2009. Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat. Rev. Genet. 10:43-55
124. Zhu KJ, Yin XY, Tang XF, Zhang FY, Yang S, Zhang XJ. 2012. Meta-Analysis of NOD2/CARD15 polymorphisms with psoriasis and psoriatic arthritis. Rheumatol. Int. 32:1893-900
125. Zuk O, Hechter E, Sunyaev SR, Lander ES. 2012. The mystery of missing heritability: Genetic interactions create phantom heritability. Proc. Natl. Acad. Sci. USA 109:1193-98