Unlabelled: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates.
Conclusion: We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121050 | PMC |
| http://dx.doi.org/10.1002/hep.24307 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Childhood idiopathic nephrotic syndrome: recent advancements shaping future guidelines.
Pediatr Nephrol
December 2024
Néphrologie Pédiatrique, Centre de Référence du Syndrome Néphrotique Idiopathique de L'enfant Et L'adulte, Hôpital Necker - Enfants Malades, APHP, Inserm U1163, Institut Imagine, Université Paris Cité, Paris, France.
Childhood idiopathic nephrotic syndrome is an important pediatric kidney disease associated with significant morbidities and even mortality. Several guidelines have been developed to standardize the terminology and patient care among the pediatric nephrology community. Since the publication of these guidelines, there have been major breakthroughs in the disease management and the understanding of underlying pathogenesis through multi-omics investigations, including the identification of anti-nephrin autoantibodies, genetic susceptibility loci, and the pathogenic role of B cell subsets.
View Article and Find Full Text PDFDisease Modules Associated with Unfavorable Sleep Patterns and Their Genetic Determinants: A Prospective Cohort Study of the UK Biobank.
Phenomics
October 2024
Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, 610000 China.
Unlabelled: Despite the established associations between sleep-related traits and major diseases, comprehensive assessment on affected disease modules and their genetic determinants is lacking. Using multiple correspondence analysis and the k-means clustering algorithm, 235,826 eligible participants were clustered into distinct unfavorable sleep patterns [short sleep duration ( = 10,073), snoring (22,419), insomnia (102,771), insomnia and snoring (62,909)] and favorable sleep pattern groups (37,654). The associations of unfavorable sleep patterns with 134 diseases were estimated using Cox regression models; and comorbidity network analyses were applied for disease module identification.
View Article and Find Full Text PDFIdentification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.
CNS Neurosci Ther
December 2024
The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Background: Previous research has demonstrated correlations between the complex types and functions of brain cells and the etiology of glioma. However, the causal relationship between gene expression regulation in specific brain cell types and glioma risk, along with its therapeutic implications, remains underexplored.
Methods: Utilizing brain cell type-specific cis-expression quantitative trait loci (cis-eQTLs) and glioma genome-wide association study (GWAS) datasets in conjunction with Mendelian randomization (MR) and colocalization analyses, we conducted a systematic investigation to determine whether an association exists between the gene expression of specific brain cell types and the susceptibility to glioma, including its subtypes.
Integration of multi-omics transcriptome-wide analysis for the identification of novel therapeutic drug targets in diabetic retinopathy.
J Transl Med
December 2024
Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, China.
Background: Diabetic retinopathy (DR) is the most important complication of Type 2 Diabetes (T2D) in eyes. Despite its prevalence, the early detection and management of DR continue to pose considerable challenges. Our research aims to elucidate potent drug targets that could facilitate the identification of DR and propel advancements in its therapeutic strategies.
View Article and Find Full Text PDFAn atlas of the shared genetic architecture between atopic and gastrointestinal diseases.
Commun Biol
December 2024
Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn's disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4 T cells consistently across relevant tissues.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!