Cargando…
Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study
BACKGROUND: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome w...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209466/ https://www.ncbi.nlm.nih.gov/pubmed/21995314 http://dx.doi.org/10.1186/1471-2350-12-139 |
_version_ | 1782215672431902720 |
---|---|
author | Andersen, Vibeke Ernst, Anja Sventoraityte, Jurgita Kupcinskas, Limas Jacobsen, Bent A Krarup, Henrik B Vogel, Ulla Jonaitis, Laimas Denapiene, Goda Kiudelis, Gediminas Balschun, Tobias Franke, Andre |
author_facet | Andersen, Vibeke Ernst, Anja Sventoraityte, Jurgita Kupcinskas, Limas Jacobsen, Bent A Krarup, Henrik B Vogel, Ulla Jonaitis, Laimas Denapiene, Goda Kiudelis, Gediminas Balschun, Tobias Franke, Andre |
author_sort | Andersen, Vibeke |
collection | PubMed |
description | BACKGROUND: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. METHODS: Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ(2), Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. RESULTS: The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant P(BD )was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively). No SNP reached genome-wide significance in the combined analyses of all the panels. CONCLUSIONS: This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between the Nordic and the other European populations. |
format | Online Article Text |
id | pubmed-3209466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32094662011-11-06 Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study Andersen, Vibeke Ernst, Anja Sventoraityte, Jurgita Kupcinskas, Limas Jacobsen, Bent A Krarup, Henrik B Vogel, Ulla Jonaitis, Laimas Denapiene, Goda Kiudelis, Gediminas Balschun, Tobias Franke, Andre BMC Med Genet Research Article BACKGROUND: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. METHODS: Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ(2), Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. RESULTS: The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant P(BD )was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively). No SNP reached genome-wide significance in the combined analyses of all the panels. CONCLUSIONS: This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between the Nordic and the other European populations. BioMed Central 2011-10-13 /pmc/articles/PMC3209466/ /pubmed/21995314 http://dx.doi.org/10.1186/1471-2350-12-139 Text en Copyright ©2011 Andersen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Andersen, Vibeke Ernst, Anja Sventoraityte, Jurgita Kupcinskas, Limas Jacobsen, Bent A Krarup, Henrik B Vogel, Ulla Jonaitis, Laimas Denapiene, Goda Kiudelis, Gediminas Balschun, Tobias Franke, Andre Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study |
title | Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study |
title_full | Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study |
title_fullStr | Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study |
title_full_unstemmed | Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study |
title_short | Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study |
title_sort | assessment of heterogeneity between european populations: a baltic and danish replication case-control study of snps from a recent european ulcerative colitis genome wide association study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209466/ https://www.ncbi.nlm.nih.gov/pubmed/21995314 http://dx.doi.org/10.1186/1471-2350-12-139 |
work_keys_str_mv | AT andersenvibeke assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT ernstanja assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT sventoraitytejurgita assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT kupcinskaslimas assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT jacobsenbenta assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT kraruphenrikb assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT vogelulla assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT jonaitislaimas assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT denapienegoda assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT kiudelisgediminas assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT balschuntobias assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy AT frankeandre assessmentofheterogeneitybetweeneuropeanpopulationsabalticanddanishreplicationcasecontrolstudyofsnpsfromarecenteuropeanulcerativecolitisgenomewideassociationstudy |