scholarly journals Genome-wide association studies in Crohn's disease: Past, present and future

2018 ◽  
Vol 7 (1) ◽  
pp. e1001 ◽  
Author(s):  
Bram Verstockt ◽  
Kenneth GC Smith ◽  
James C Lee
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals

2018 ◽  
Vol 13 (5) ◽  
pp. 648-658 ◽  
Author(s):  
Yoichi Kakuta ◽  
Yosuke Kawai ◽  
Takeo Naito ◽  
Atsushi Hirano ◽  
Junji Umeno ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Genome Wide Association ◽  
Effector Memory ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

Abstract Background and Aims Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel. Methods Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions. Results Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10−6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10−8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression. Conclusions RAP1A is a novel susceptibility locus for CD in the Japanese population.

Association between genome-wide association studies reported SNPs and pediatric-onset Crohn’s disease in Canadian children

2010 ◽  
Vol 128 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Devendra K. Amre ◽  
David R. Mack ◽  
Kenneth Morgan ◽  
David Israel ◽  
Colette Deslandres ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Pediatric Onset

scholarly journals SEARCH OF TUBERCULOSIS SUSCEPTIBILITY GENES USING THE RESULTS OF GENOME-WIDE ASSOCIATION STUDY OF CROHN’S DISEASE

2013 ◽  
Vol 12 (3) ◽  
pp. 61-68
Author(s):  
A. A. Rudko ◽  
M. B. Freidin ◽  
Ye. Yu. Bragina ◽  
A. R. An ◽  
V. P. Puzyryov
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Susceptibility Factors ◽  
First Time

Crohn’s disease (CD) and tuberculosis (TB) share several mechanisms of pathogenesis, and this suggests they also have common genetic susceptibility factors. To test this hypothesis, we performed the analysis of association between TB and polymorphisms of genes associated with CD, according to the results of genome-wide association studies, in Russians from Tomsk and indigenous people from Tuva. For the first time, The rs2872507 (ORMDL3), rs3810936 (TNFSF15), rs10192702 (ATG16L1), rs9286879 (1q24.3), rs10507523 (13q14.11) polymorphisms were found to be associated with TB in Russians. The rs1407308 (TNFSF15) and rs1736135 (21q21.1) were associated with the disease in Tuvinians. The associations found are likely due to the functional role of the relevant proteins and their pathogenetic influence on the immune reaction underlying tuberculosis infection. Overall, the study of polymorphisms associated with CD allowed us to identify new candidate genes for TB.

scholarly journals Mediated pleiotropy between psychiatric disorders and autoimmune disorders revealed by integrative analysis of multiple GWAS

2015 ◽  
Author(s):  
Qian Wang ◽  
Can Yang ◽  
Joel Gelernter ◽  
Hongyu Zhao
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Psychiatric Disorders ◽  
Association Studies ◽  
Autoimmune Disorders ◽  
Integrative Analysis ◽  
Genome Wide Association Studies ◽  
Immune Disorder ◽  
Genome Wide ◽  
Immunological Mechanisms

Epidemiological observations and molecular-level experiments have indicated that brain disorders in the realm of psychiatry may be influenced by immune dysregulation. However, the degree of genetic overlap between immune disorders and psychiatric disorders has not been well established. We investigated this issue by integrative analysis of genome-wide association studies (GWAS) of 18 complex human traits/diseases (five psychiatric disorders, seven autoimmune disorders, and others) and multiple genome-wide annotation resources (Central nervous system genes, immune-related expression-quantitative trait loci (eQTL) and DNase I hypertensive sites from 98 cell-lines). We detected pleiotropy in 24 of the 35 psychiatric-autoimmune disorder pairs, with statistical significance as strong as p=3.9e-285 (schizophrenia-rheumatoid arthritis). Strong enrichment (>1.4 fold) of immune-related eQTL was observed in four psychiatric disorders. Genomic regions responsible for pleiotropy between psychiatric disorders and autoimmune disorders were detected. The MHC region on chromosome 6 appears to be the most important (and it was indeed previously noted (1-3) as a confluence between schizophrenia and immune disorder risk regions), with many other regions, such as cytoband 1p13.2. We also found that most alleles shared between schizophrenia and Crohn's disease have the same effect direction, with similar trend found for other disorder pairs, such as bipolar-Crohn's disease. Our results offer a novel bird's-eye view of the genetic relationship and demonstrate strong evidence for mediated pleiotropy between psychiatric disorders and autoimmune disorders. Our findings might open new routes for prevention and treatment strategies for these disorders based on a new appreciation of the importance of immunological mechanisms in mediating risk.

scholarly journals The Interplay of Genes with the Gut Microbiota in the Aetiopathogenesis of Spondyloarthropathies and Crohn’s Disease: Implications for Future Therapeutic Targets

2021 ◽  
pp. 140-151
Author(s):  
Simon Stebbings ◽  
Rebecca Roberts
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Association Studies ◽  
Therapeutic Targets ◽  
Genome Wide Association Studies ◽  
Host Genetics ◽  
Genome Wide ◽  
Shared Genetic

The phenotypical overlap between the spondyloarthropathies (SpA) and Crohn’s disease (CD) has long been recognised. More recently, the co-inheritance of these diseases and the existence of a plethora of shared genetic risk loci have been demonstrated by genealogic databases and genome-wide association studies. Now there is mounting evidence to suggest that the interplay between the gut microbiota and host genetics is central to the shared aetiopathogenesis of SpA and CD. The clinical management of patients with both SpA and CD can be challenging. Preliminary studies seeking to understand this interplay have identified novel therapeutic targets and approaches, which may, in the future, significantly advance patient care. This review provides an overview of the role of host genetics and the intestinal microbiota in the shared aetiopathogenesis of SpA and CD, and explores how this interplay can advance the search for new therapeutic targets.

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