scholarly journals Genetic overlap between Parkinson disease and inflammatory bowel disease

2022 ◽  
Author(s):  
Xiaoying Kang ◽  
Alexander Ploner ◽  
Yunzhang Wang ◽  
Jonas F Ludvigsson ◽  
Dylan M Williams ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Parkinson Disease ◽  
Bowel Disease ◽  
Association Studies ◽  
Genetic Correlations ◽  
Genome Wide Association Studies ◽  
High Definition ◽  
Genetic Overlap ◽  
Common Etiology ◽  
Inflammatory Bowel

Importance Parkinson disease (PD) and inflammatory bowel disease (IBD) have been associated, implying shared pathophysiology. Characterizing genetic pleiotropy between the two conditions aids the exploration of common etiology. Objective To estimate the genetic correlation between PD and IBD and to identify specific loci influencing both conditions. Design Genetic study with applications of high definition likelihood and conditional false discovery rate (FDR) framework. Setting The study was based on summary statistics of genome-wide association studies (GWAS). Participants The PD GWAS comprised 37,688 cases and 981,372 controls, and the IBD GWAS included 25,042 cases and 34,915 controls. Participants were of mixed ethnicity. Exposures None. Main Outcomes and Measures The main outcomes were a set of single nucleotide polymorphisms (SNPs) identified by conditional FDR analysis as jointly associated with PD and IBD. Results Weak but statistically significant genetic correlations were detected for PD with both Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of IBD. A total of 1333 SNPs in 28 genomic loci and 1915 SNPs in 22 loci were jointly associated with PD-CD and PD-UC, respectively, at conjunctional FDR under 0.01. The pleiotropic loci appeared distinctive for PD-CD and PD-UC, are mostly novel and comprise loci with either same or opposing genetic effects on the two phenotypes. Positional and eQTL mapping prioritized 316 PD-CD and 303 PD-UC genes, among which only <10% are differentially expressed in both colon and substantia nigra. The KEGG pathways enriched by all prioritized genes were highly concordant between PD-CD and PD-UC, with the majority being related to immune and/or autoimmune dysfunction. Conclusions and Relevance Overall, we found robust evidence for a genetic link between PD and each subtype of IBD. The identified genetic overlap is complex at the locus and gene levels, indicating the presence of both common etiology and antagonistic pleiotropy. At the functional level, our results highlighted a central role of host immunity and/or autoimmunity in the PD-IBD relationship.

Very early onset inflammatory bowel disease (VEO-IBD); spectrum of clinical presentation, diagnostic tools and outcome in children

2021 ◽  
Vol 71 (10) ◽  
pp. 2350-2354
Author(s):  
Huma Arshad Cheema ◽  
Nadia Waheed ◽  
Anjum Saeed ◽  
Zafar Fayyaz ◽  
Muhammad Nadeem Anjum ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Clinical Presentation ◽  
Association Studies ◽  
Diagnostic Tools ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Basic Work ◽  
Inflammatory Bowel

Background: Very early-onset inflammatory bowel disease (VEO-IBD) is defined as diagnosis of Ulcerative Colitis (UC) or Crohn’s Disease (CD) in children under six years of age. Genome wide association studies have linked a strong genetic component responsible for VEO-IBD. Approximately, 30-40% children of VEO-IBD have underlying immunodeficiency states. We aimed to study the spectrum of presentation, underlying monogenetic defects and outcome in VEO-IBD. Methods: This is a prospective, observational study conducted at division of Gastroenterology, the Children's Hospital & the Institute of Child Health, Lahore, over 2 years. Children developing features of IBD under six-years of age were included. Data included demography, clinical presentation, diagnostic tools and outcome. Gastroscopy and colonoscopy were performed in all patients in addition to basic work up done for associatedimmunodeficiency states and molecular genetics.  SPSS version 21 was used for analysis. Continuous...

scholarly journals Application of Proteomics to Inflammatory Bowel Disease Research: Current Status and Future Perspectives

2019 ◽  
Vol 2019 ◽  
pp. 1-24 ◽  
Author(s):  
Arash Assadsangabi ◽  
Caroline A. Evans ◽  
Bernard M. Corfe ◽  
Alan Lobo
Keyword(s):  
Inflammatory Bowel Disease ◽  
Cancer Progression ◽  
Bowel Disease ◽  
Biomarker Discovery ◽  
Association Studies ◽  
Disease Process ◽  
Current Status ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a chronic relapsing/remitting inflammatory illness of the gastrointestinal tract of unknown aetiology. Despite recent advances in decoding the pathophysiology of IBD, many questions regarding disease pathogenesis remain. Genome-wide association studies (GWAS) and knockout mouse models have significantly advanced our understanding of genetic susceptibility loci and inflammatory pathways involved in IBD pathogenesis. Despite their important contribution to a better delineation of the disease process in IBD, these genetic findings have had little clinical impact to date. This is because the presence of a given gene mutation does not automatically correspond to changes in its expression or final metabolic or structural effect(s). Furthermore, the existence of these gene susceptibility loci in the normal population suggests other driving prerequisites for the disease manifestation. Proteins can be considered the main functional units as almost all intracellular physiological functions as well as intercellular interactions are dependent on them. Proteomics provides methods for the large-scale study of the proteins encoded by the genome of an organism or a cell, to directly investigate the proteins and pathways involved. Understanding the proteome composition and alterations yields insights into IBD pathogenesis as well as identifying potential biomarkers of disease activity, mucosal healing, and cancer progression. This review describes the state of the art in the field with respect to the study of IBD and the potential for translation from biomarker discovery to clinical application.

scholarly journals Identifying novel high-impact rare disease-causing mutations, genes and pathways in exomes of Ashkenazi Jewish inflammatory bowel disease patients

2020 ◽  
Author(s):  
Yiming Wu ◽  
Kyle Gettler ◽  
Mamta Giri ◽  
Dalin Li ◽  
Cigdem Sevim Bayrak ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Association Studies ◽  
High Impact ◽  
Genomic Research ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Common Genetic Variants ◽  
Inflammatory Bowel ◽  
Shared Risk

ABSTRACTInflammatory bowel disease (IBD) is a group of chronic diseases, affecting different parts of the gastrointestinal tract, that mainly comprises Crohn’s Disease (CD) and Ulcerative Colitis (UC). Most IBD genomic research to date has involved genome-wide association studies (GWAS) of common genetic variants, mostly in Europeans, resulting in the identification of over 200 risk loci. The incidence of IBD in Ashkenazi Jews (AJ) is particularly high compared to other population groups and rare protein-coding variants are significantly enriched in AJ. These variants are expected to have a larger phenotypic effect and are hypothesized to complement the missing heritability that cannot be fully addressed by GWAS in IBD. Therefore, we genetically identified 4,974 AJs IBD cases and controls from whole exome sequencing (WES) data from the NIDDK IBD Genetics Consortium (IBDGC). We selected credible rare variants with high predicted impact, aggregated them into genes, and performed gene burden and pathway enrichment analyses to identify 7 novel plausible IBD-causing genes:NCF1, CES1, ICAM1, INPP5D, ABCB1, IL33 and TLR4. We further perform bulk and single-cell RNA sequencing, demonstrating the likely relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of AJ adult IBD displays a significant overlap with very early onset IBD (VEOIBD) genetics. At the variant level, we performed Phenome-wide association studies (PheWAS) in the UK Biobank to replicate risk sites in IBD and reveal shared risk sites with other diseases. Finally, we showed that a polygenic risk score (PRS) has high power to differentiate AJ IBD cases from controls when using rare and high impact variants.

scholarly journals Lymphocyte Antigen 75 Polymorphisms Are Associated with Disease Susceptibility and Phenotype in Japanese Patients with Inflammatory Bowel Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Atsuhiro Hirayama ◽  
Satoru Joshita ◽  
Kei Kitahara ◽  
Kenji Mukawa ◽  
Tomoaki Suga ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Association Studies ◽  
Japanese Patients ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Lymphocyte Antigen ◽  
Genome Wide ◽  
Surgical History ◽  
Inflammatory Bowel

Recent genome-wide association studies have rapidly improved our understanding of the molecular pathways leading to inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC). Although several reports have demonstrated that gene single nucleotide polymorphisms (SNPs) are associated with susceptibility to IBD, its precise genetic factors have not been fully clarified. Here, we performed an association analysis between lymphocyte antigen 75 (LY75) genetic variations and IBD susceptibility or phenotype. SNPs were genotyped in 51 CD patients, 94 UC patients, and 269 healthy controls of Japanese ethnicity. We detected a significant relationship with CD susceptibility for the rs16822581 LY75 SNP (P=0.045). One haplotype (GT, P=0.042) was also associated with CD susceptibility, while another carrying the opposite SNP (CA) was linked to an absence of surgical history for CD. Our findings confirm that LY75 is involved in CD susceptibility and may play a role in disease activity in the Japanese population.

scholarly journals Molecular Profiling of Inflammatory Bowel Disease: Is It Ready for Use in Clinical Decision-Making?

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 535 ◽  
Author(s):  
Ho-Su Lee ◽  
Isabelle Cleynen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Clinical Decision Making ◽  
Association Studies ◽  
Disease Onset ◽  
Molecular Profiling ◽  
Response To Therapy ◽  
Current Status ◽  
Genome Wide Association Studies ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) is a heterogeneous disorder in terms of age at onset, clinical phenotypes, severity, disease course, and response to therapy. This underlines the need for predictive and precision medicine that can optimize diagnosis and disease management, provide more cost-effective strategies, and minimize the risk of adverse events. Ideally, we can leverage molecular profiling to predict the risk to develop IBD and disease progression. Despite substantial successes of genome-wide association studies in the identification of genetic variants affecting IBD susceptibility, molecular profiling of disease onset and progression as well as of treatment responses has lagged behind. Still, thanks to technological advances and good study designs, predicting phenotypes using genomics and transcriptomics in IBD has been rapidly evolving. In this review, we summarize the current status of prediction of disease risk, clinical course, and response to therapy based on clinical case presentations. We also discuss the potential and limitations of the currently used approaches.

scholarly journals Genome-wide association studies of inflammatory bowel disease in German shepherd dogs

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200685 ◽  
Author(s):  
Atiyeh Peiravan ◽  
Francesca Bertolini ◽  
Max F. Rothschild ◽  
Kenneth W. Simpson ◽  
Albert E. Jergens ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
German Shepherd ◽  
Genome Wide ◽  
Inflammatory Bowel

Identification of three novel susceptibility loci for inflammatory bowel disease in Koreans in an extended genome-wide association study

2021 ◽  
Author(s):  
Seulgi Jung ◽  
Byong Duk Ye ◽  
Ho-Su Lee ◽  
Jiwon Baek ◽  
Gyeonghoon Kim ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Data Set ◽  
Genome Wide ◽  
Inflammatory Bowel

Abstract Background and Aims Genome-wide association studies (GWAS) of inflammatory bowel disease (IBD) in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify 2 new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional data set of 1,726 cases and 378 controls. Methods An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3,195 cases and 4,419 controls, followed by replication in an additional 1,088 cases and 845 controls. Results The meta-analysis of Korean GWAS identified 1 novel locus for ulcerative colitis at rs76227733 on 10q24 (pcombined = 6.56 × 10 -9) and 2 novel loci for Crohn’s disease (CD) at rs2240751 on 19p13 (pcombined = 3.03 × 10 -8) and rs6936629 in on 6q22 (pcombined = 3.63 × 10 -8). Pathway-based analysis of GWAS data using MAGMA showed that MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14 % of variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population. Conclusions The identification of novel loci not previously associated with IBD suggest the importance of studying the inflammatory bowel disease genetics in diverse populations.

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