title: Replication study of ulcerative colitis risk loci in a Lithuanian-Latvian case-control sample.
abstract: BACKGROUND
  Differences between populations might be reflected in their different genetic risk maps to complex diseases, for example, inflammatory bowel disease. We here investigated the role of known inflammatory bowel disease-associated single nucleotide polymorphisms (SNPs) in a subset of patients with ulcerative colitis (UC) from the Northeastern European countries Lithuania and Latvia and evaluated possible epistatic interactions between these genetic variants.
  
  
  METHODS
  We investigated 77 SNPs derived from 5 previously published genome-wide association studies for Crohn's disease and UC. Our study panel comprised 444 Lithuanian and Latvian patients with UC and 1154 healthy controls. Single marker case-control association and SNP-SNP epistasis analyses were performed.
  
  
  RESULTS
  We found 14 SNPs tagging 9 loci, including 21q21.1, NKX2-3, MST1, the HLA region, 1p36.13, IL10, JAK2, ORMDL3, and IL23R, to be associated with UC. Interestingly, the association of UC with previously identified variants in the HLA region was not the strongest association in our study (P = 4.34 × 10, odds ratio [OR] = 1.25), which is in contrast to all previously published studies. No association with any disease subphenotype was found. SNP-SNP interaction analysis showed significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes and increased risk for UC (P = 1.64 × 10, OR = 2.44). The association has been confirmed in the Danish study group (P = 0.04, OR = 3.25).
  
  
  CONCLUSIONS
  We confirmed the association of the 9 loci (21q21.1, 1p36.13, NKX2-3, MST1, the HLA region, IL10, JAK2, ORMDL3, and IL23R) with UC in the Lithuanian-Latvian population. SNP-SNP interaction analyses showed that the combination of SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk for UC.
authors: *Institute for Digestive Research and †Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania; ‡Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany; §Center of Hepatology, Gastroenterology and Dietetics, Vilnius University, Vilnius, Lithuania; ¶Digestive Diseases Centre GASTRO, Riga, Latvia; Departments of ‖Children Diseases and **Health Management, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania; ††Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark; ‡‡Medical Department, Hospital of Southern Jutland, Aabenraa, Denmark; §§Internal Disease Department, Riga Stradins University, Riga, Latvia; and ¶¶Department of Surgery, Academy of Medicine, Lithuanian University of Health Science, Kaunas, Lithuania.
authors: Jurgita
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authors: Kiudelis
authors: Eva
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authors: Ellinghaus
authors: Tobias
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authors: Balschun
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authors: Zvirbliene
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authors: Denapiene
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authors: Pranculiene
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authors: Ellinghaus
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authors: Valantinas
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authors: Irnius
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authors: Derovs
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authors: Tamelis
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authors: Schreiber
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authors: Kupcinskas
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mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22