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Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci
BACKGROUND: Genome-wide association studies of two main forms of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), have identified 99 susceptibility loci, but these explain only ∼23% of the genetic risk. Part of the ‘hidden heritability’ could be in transmissible g...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459955/ https://www.ncbi.nlm.nih.gov/pubmed/23028907 http://dx.doi.org/10.1371/journal.pone.0045287 |
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author | Fransen, Karin Mitrovic, Mitja van Diemen, Cleo C. B.K., Thelma Sood, Ajit Franke, Andre Schreiber, Stefan Midha, Vandana Juyal, Garima Potocnik, Uros Fu, Jingyuan Nolte, Ilja Weersma, Rinse K. |
author_facet | Fransen, Karin Mitrovic, Mitja van Diemen, Cleo C. B.K., Thelma Sood, Ajit Franke, Andre Schreiber, Stefan Midha, Vandana Juyal, Garima Potocnik, Uros Fu, Jingyuan Nolte, Ilja Weersma, Rinse K. |
author_sort | Fransen, Karin |
collection | PubMed |
description | BACKGROUND: Genome-wide association studies of two main forms of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), have identified 99 susceptibility loci, but these explain only ∼23% of the genetic risk. Part of the ‘hidden heritability’ could be in transmissible genetic effects in which mRNA expression in the offspring depends on the parental origin of the allele (genomic imprinting), since children whose mothers have CD are more often affected than children with affected fathers. We analyzed parent-of-origin (POO) effects in Dutch and Indian cohorts of IBD patients. METHODS: We selected 28 genetic loci associated with both CD and UC, and tested them for POO effects in 181 Dutch IBD case-parent trios. Three susceptibility variants in NOD2 were tested in 111 CD trios and a significant finding was re-evaluated in 598 German trios. The UC-associated gene, BTNL2, reportedly imprinted, was tested in 70 Dutch UC trios. Finally, we used 62 independent Indian UC trios to test POO effects of five established Indian UC risk loci. RESULTS: We identified POO effects for NOD2 (L1007fs; OR = 21.0, P-value = 0.013) for CD; these results could not be replicated in an independent cohort (OR = 0.97, P-value = 0.95). A POO effect in IBD was observed for IL12B (OR = 3.2, P-value = 0.019) and PRDM1 (OR = 5.6, P-value = 0.04). In the Indian trios the IL10 locus showed a POO effect (OR = 0.2, P-value = 0.03). CONCLUSIONS: Little is known about the effect of genomic imprinting in complex diseases such as IBD. We present limited evidence for POO effects for the tested IBD loci. POO effects explain part of the hidden heritability for complex genetic diseases but need to be investigated further. |
format | Online Article Text |
id | pubmed-3459955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34599552012-10-01 Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci Fransen, Karin Mitrovic, Mitja van Diemen, Cleo C. B.K., Thelma Sood, Ajit Franke, Andre Schreiber, Stefan Midha, Vandana Juyal, Garima Potocnik, Uros Fu, Jingyuan Nolte, Ilja Weersma, Rinse K. PLoS One Research Article BACKGROUND: Genome-wide association studies of two main forms of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), have identified 99 susceptibility loci, but these explain only ∼23% of the genetic risk. Part of the ‘hidden heritability’ could be in transmissible genetic effects in which mRNA expression in the offspring depends on the parental origin of the allele (genomic imprinting), since children whose mothers have CD are more often affected than children with affected fathers. We analyzed parent-of-origin (POO) effects in Dutch and Indian cohorts of IBD patients. METHODS: We selected 28 genetic loci associated with both CD and UC, and tested them for POO effects in 181 Dutch IBD case-parent trios. Three susceptibility variants in NOD2 were tested in 111 CD trios and a significant finding was re-evaluated in 598 German trios. The UC-associated gene, BTNL2, reportedly imprinted, was tested in 70 Dutch UC trios. Finally, we used 62 independent Indian UC trios to test POO effects of five established Indian UC risk loci. RESULTS: We identified POO effects for NOD2 (L1007fs; OR = 21.0, P-value = 0.013) for CD; these results could not be replicated in an independent cohort (OR = 0.97, P-value = 0.95). A POO effect in IBD was observed for IL12B (OR = 3.2, P-value = 0.019) and PRDM1 (OR = 5.6, P-value = 0.04). In the Indian trios the IL10 locus showed a POO effect (OR = 0.2, P-value = 0.03). CONCLUSIONS: Little is known about the effect of genomic imprinting in complex diseases such as IBD. We present limited evidence for POO effects for the tested IBD loci. POO effects explain part of the hidden heritability for complex genetic diseases but need to be investigated further. Public Library of Science 2012-09-27 /pmc/articles/PMC3459955/ /pubmed/23028907 http://dx.doi.org/10.1371/journal.pone.0045287 Text en © 2012 Fransen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fransen, Karin Mitrovic, Mitja van Diemen, Cleo C. B.K., Thelma Sood, Ajit Franke, Andre Schreiber, Stefan Midha, Vandana Juyal, Garima Potocnik, Uros Fu, Jingyuan Nolte, Ilja Weersma, Rinse K. Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci |
title | Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci |
title_full | Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci |
title_fullStr | Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci |
title_full_unstemmed | Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci |
title_short | Limited Evidence for Parent-of-Origin Effects in Inflammatory Bowel Disease Associated Loci |
title_sort | limited evidence for parent-of-origin effects in inflammatory bowel disease associated loci |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459955/ https://www.ncbi.nlm.nih.gov/pubmed/23028907 http://dx.doi.org/10.1371/journal.pone.0045287 |
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