A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at<i>RBX1-EP300</i>

Juliá, Antonio; Domènech, Eugeni; Ricart, Elena; Tortosa, Raül; García–Sánchez, Valle; Gisbert, Javier P.; Mateu, Pilar Nos; Gutiérrez, Ana; Gomollón, Fernando; Mendoza, Juan L.; García‐Planella, Esther; Acosta, Manuel Barreiro‐de; Muñoz, Fernándo; Vera, Maribel; Saro, Cristina; Esteve, María; Andreu, Montserrat; Alonso, Arnald; López-Lasanta, María; Codó, Laia; Gelpí, Josep Lluís; García‐Montero, Andrés C.; Bertranpetit, Jaume; Absher, Devin; Panés, Julián; Marsal, Sara

doi:10.1136/gutjnl-2012-302865

Cited by 43 publications

(24 citation statements)

References 40 publications

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“…Genetic variability at 5p13 also contributes to other diseases with inflammatory components, including Crohn's disease, ulcerative colitis, ankylosing spondylitis and multiple sclerosis . Furthermore, cis‐regulatory effects involving the expression of PTGER4 in some of these traits have been described previously in lymphoblastoid cell lines .…”

Section: Discussionmentioning

confidence: 91%

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

et al. 2018

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Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine‐mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 × 10−04) and on chromosome 8q24 at rs2585176 (P = 1.09 × 10−09). On chromosome 5p13 we found cis‐eQTL effects with an upregulation of PTGER4 expression in GC risk allele carrier (P = 9.27 × 10−11). On chromosome 8q24 we observed cis‐eQTL effects with an upregulation of PSCA expression in GC risk allele carrier (P = 2.17 × 10−47). In addition, we found trans‐eQTL effects for the same variants on 8q24 with a downregulation of MBOAT7 expression in GC risk allele carrier (P = 3.11 × 10−09). In summary, we confirmed and refined the previously reported GC associations at both chromosomal regions. Our data point to shared etiological factors between Asians and Europeans. Furthermore, our data imply an upregulated expression of PTGER4 and PSCA as well as a downregulated expression of MBOAT7 in gastric tissue as risk‐conferring GC pathomechanisms.

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Section: Discussionmentioning

confidence: 91%

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

et al. 2018

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“…Therefore, we performed an LD analysis of the identified SNVs with the SNVs located on adjacent non-coding regions that were identified in previous GWASs (see online supplementary table S7). In the LD analysis, rs12994997 ,59 rs3792109 ,60 rs3828309 34 and rs10210302 ,61 which were found in the non-coding region of the ATG16L1 gene, were reported in a Japanese (JPT) and Han Chinese (CHB) population in the 1000 Genomes Database, and these SNVs are all in strong LD (R 2 >0.8) with rs2241880 . Therefore, we performed combined annotation dependent depletion analysis on these variants, and rs2241880 was predicted to be in the top 10% most deleterious substitutions in the human genome.…”

Section: Discussionmentioning

confidence: 99%

Deep resequencing of 131 Crohn's disease associated genes in pooled DNA confirmed three reported variants and identified eight novel variants

Hong

Park

et al. 2015

Gut

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“…TNF super family, HLA, HLA-A, MIC1, AIF1, LTA, etc.) in the predisposition to CD in humans has been demonstrated or suggested [19], [63], [64], [65]. ARS-BFGL-NGS-11887 is located in the intronic region of TCF19 (transcription factor 19) which is highly conserved among multiple species.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Analysis and Genomic Prediction of Mycobacterium avium Subspecies paratuberculosis Infection in US Jersey Cattle

et al. 2014

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Paratuberculosis (Johne’s disease), an enteric disorder in ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), causes economic losses in excess of $200 million annually to the US dairy industry. To identify genomic regions underlying susceptibility to MAP infection in Jersey cattle, a case-control genome-wide association study (GWAS) was performed. Blood and fecal samples were collected from ∼5,000 mature cows in 30 commercial Jersey herds from across the US. Discovery data consisted of 450 cases and 439 controls genotyped with the Illumina BovineSNP50 BeadChip. Cases were animals with positive ELISA and fecal culture (FC) results. Controls were animals negative to both ELISA and FC tests that matched cases on birth date and herd. Validation data consisted of 180 animals including 90 cases (positive to FC) and 90 controls (negative to ELISA and FC), selected from discovery herds and genotyped by Illumina BovineLD BeadChip (∼7K SNPs). Two analytical approaches were used: single-marker GWAS using the GRAMMAR-GC method and Bayesian variable selection (Bayes C) using GenSel software. GRAMMAR-GC identified one SNP on BTA7 at 68 megabases (Mb) surpassing a significance threshold of 5×10−5. ARS-BFGL-NGS-11887 on BTA23 (27.7 Mb) accounted for the highest percentage of genetic variance (3.3%) in the Bayes C analysis. SNPs identified in common by GRAMMAR-GC and Bayes C in both discovery and combined data were mapped to BTA23 (27, 29 and 44 Mb), 3 (100, 101, 106 and 107 Mb) and 17 (57 Mb). Correspondence between results of GRAMMAR-GC and Bayes C was high (70–80% of most significant SNPs in common). These SNPs could potentially be associated with causal variants underlying susceptibility to MAP infection in Jersey cattle. Predictive performance of the model developed by Bayes C for prediction of infection status of animals in validation set was low (55% probability of correct ranking of paired case and control samples).

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A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus atRBX1-EP300

Abstract: In this GWAS performed on a southern European cohort, we have identified a new risk locus for CD between RBX1 and EP300. This study demonstrates that using populations of different ancestry is a useful strategy to identify new risk loci for CD.

Cited by 43 publications

References 40 publications

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Evidence for PTGER4,PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level

Deep resequencing of 131 Crohn's disease associated genes in pooled DNA confirmed three reported variants and identified eight novel variants

Genome-Wide Association Analysis and Genomic Prediction of Mycobacterium avium Subspecies paratuberculosis Infection in US Jersey Cattle

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