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 Prioritization of genes associated with the pathogenesis of leukosis in cattle

2019 ◽  
Vol 22 (8) ◽  
pp. 1063-1069 ◽  
Author(s):  
N. S. Yudin ◽  
N. L. Podkolodnyy ◽  
T. A. Agarkova ◽  
E. V. Ignatieva
Keyword(s):  
Protein Interactions ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Mammalian Species ◽  
Genome Wide Association ◽  
Farm Animals ◽  
Genome Wide Association Studies ◽  
Protein Protein Interactions ◽  
Genome Wide ◽  
A Genome

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF,LTB,BOLA-DQA1,BOLA-DRB3,ATF2), which can affect the sensitivity/resistance of cattle to leukemia.

scholarly journals Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry

2018 ◽  
Vol 28 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Sara L Pulit ◽  
Charli Stoneman ◽  
Andrew P Morris ◽  
Andrew R Wood ◽  
Craig A Glastonbury ◽  
...  
Keyword(s):  
Body Fat ◽  
Association Studies ◽  
Meta Analysis ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.

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