TY - JOUR
T1 - Replication study of ulcerative colitis risk loci in a Lithuanian-Latvian case control sample
AU - Skieceviciene, Jurgita
AU - Kiudelis, Gediminas
AU - Ellinghaus, Eva
AU - Balschun, Tobias
AU - Jonaitis, Laimas V.
AU - Zvirbliene, Aida
AU - Denapiene, Goda
AU - Leja, Marcis
AU - Pranculiene, Gitana
AU - Kalibatas, Vytenis
AU - Saadati, Hamidreza
AU - Ellinghaus, David
AU - Andersen, Vibeke
AU - Valantinas, Jonas
AU - Irnius, Algimantas
AU - Derovs, Aleksejs
AU - Tamelis, Algimantas
AU - Schreiber, Stefan
AU - Kupcinskas, Limas
AU - Franke, Andre
PY - 2013/10
Y1 - 2013/10
N2 - 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 × 1023, 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 × 1026, 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.
AB - 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 × 1023, 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 × 1026, 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.
KW - Case control
KW - Lithuanian-Latvian
KW - Single nucleotide polymorphisms
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=84888263784&partnerID=8YFLogxK
U2 - 10.1097/MIB.0b013e3182a3eaeb
DO - 10.1097/MIB.0b013e3182a3eaeb
M3 - Article
C2 - 23974994
AN - SCOPUS:84888263784
SN - 1078-0998
VL - 19
SP - 2349
EP - 2355
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 11
ER -