20.500.12556/DKUM-50494 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), Crohnʼs disease (CD) and ulcerative colitis (UC), have identified 99 susceptibility loci, but these explain only ~23% of the genetic risk. Part of the Žhidden heritabilityʼ 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 testedthem 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. inflammatory bowel diseases IBD genetic locus genetics kronična vnetna črevesna bolezen KVČB genski lokus genetika true false true Angleški jezik Slovenski jezik Znanstveno delo 2015-07-10 12:40:42 2015-07-10 12:40:42 2022-05-29 03:07:08 2022-03-30 03:07:05 2012 0 0 str. 1-8 št. 9 Letn. 7 2012 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1932-6203 616.34-002 2005896 512221240 10.1371/journal.pone.0045287 1932-6203 URN:SI:UM:DK:TAB6IGGS PLoS_ONE_2012_Fransen_et_al._Limited_Evidence_for_Parent-of-Origin_Effects_in_Inflammatory_Bowel_Disease_Associated_Loci.PDF PLoS_ONE_2012_Fransen_et_al._Limited_Evidence_for_Parent-of-Origin_Effects_in_Inflammatory_Bowel_Disease_Associated_Loci.PDF 1 0B2D74273FB11572048964C40FC54250 6fc93d6f05d87d39455fb3166f85d0285e6312c492f0082315c4ebb5223121a6 42fd9656-7c0e-11eb-bb7a-00155d0001ca https://dk.um.si/Dokument.php?lang=slv&id=112747 http://dx.plos.org/10.1371/journal.pone.0045287 1 https://dk.um.si/Dokument.php?lang=slv&id=75053 Medicinska fakulteta 0 0 0