Exploring genetic associations of Crohn’s disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations
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ABSTRACT:
SUBMITTER: Yu C
PROVIDER: S-EPMC10885353 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine whether macrophage migration inhibitory factor (MIF) gene polymorphism is associated with the risk of inflammatory bowel disease (IBD).DesignSystem review and meta-analysis.MethodsMEDLINE, EMBASE, Web of Science databases, Cochrane Library and the Chinese Biomedical Literature database (CBM) were searched for the case-control trails for MIF and IBD. All the studies included in this manuscript met the inclusion and exclusion criteria. An OR analysis using a 95% CI was employed to assess the association of the MIF-173 G/C polymorphism with IBD susceptibility.ResultsThere was a significant association between the MIF-173 G/C gene polymorphism and IBD in the total population under the recessive model (CC vs GC+GG; OR=1.75, CI 1.04 to 2.95, p=0.04 for heterogeneity) and the codominant model (CC vs GG; OR=1.74, CI 1.02 to 2.97, p=0.04 for heterogeneity). In the stratified analysis by ethnicity, significantly increased risks were observed for Asians using the recessive (OR=1.75, CI 1.04 to 2.95, p=0.04 for heterogeneity) and codominant models (OR=1.74, CI 1.02 to 2.97, p=0.04 for heterogeneity). Within the subgroups of UC and CD, significant differences were observed regarding UC using the recessive (OR=1.60, CI 1.09 to 2.35, p=0.02 for heterogeneity) and codominant models (OR=1.64, CI 1.12 to 2.41, p=0.01 for heterogeneity). In the stratified analysis by ethnicity for UC, significant differences were observed regarding CC in Asians vs GC+GG (OR=1.73, CI 1.02 to 2.94, p=0.04 for heterogeneity).ConclusionsThe meta-analysis suggested that the MIF-173 G/C polymorphism contributed to the susceptibility of IBD. When considering the subgroups of ethnicity and UC and CD, the results suggested that the polymorphism is more significant for UC in Asians.
| S-EPMC3884786 | biostudies-literature
Project description:Background/aimsVedolizumab is indicated for moderately-to-severely active ulcerative colitis (UC) and Crohn's disease (CD). Because multiple factors may result in different pharmacokinetics and clinical efficacies, understanding determinants of vedolizumab clearance may enhance dose and treatment strategies. The aim was to characterize vedolizumab pharmacokinetics in Asian and non-Asian UC and CD patients.MethodsPopulation pharmacokinetic analysis for repeated measures, using data from 5 studies, was conducted using nonlinear mixed-effects modeling. A Bayesian estimation approach in NONMEM 7.3 was utilized to leverage the predominantly sparse data available for this analysis with results from a prior population pharmacokinetic analysis of vedolizumab.ResultsVedolizumab pharmacokinetics were described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half life of vedolizumab was 24.7 days for anti-vedolizumab antibody (AVA)-negative patients and 18.1 days for AVA-positive patients; linear clearance (CLL) was 0.165 L/day for AVA-negative patients and 0.246 L/day for AVA-positive patients; central (Vc) and peripheral compartment volumes of distribution were 3.16 L and 1.84 L, respectively. Interindividual variabilities (percent coefficient of variation) were 30.8% for CLL and 19% for Vc; interoccasion variability on CLL was 20.3%; residual variance was 17.8%. For albumin, body weight and AVA, only extreme values were identified as potentially clinically important predictors of CLL. The effect of race (Asian/non-Asian) and diagnosis (UC/CD) on CLL was negligible and likely not of clinical importance.ConclusionsPharmacokinetic parameters were similar in Asian and non-Asian patients with moderately-to-severely active UC and CD. This analysis supports use of vedolizumab flat-fixed dosing in these patients. (Clinicaltrials.gov Identifiers: NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2). CCT 101; NCT02039505 and CCT-001; NCT02038920).
| S-EPMC7873400 | biostudies-literature
Project description:BackgroundThe associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian populations.MethodsIndependent genetic variants strongly associated with RA in European and East Asian populations were selected as instrumental variables from genome-wide association studies of 58,284 European individuals (14,361 cases and 43,923 controls) and 22,515 East Asian individuals (4873 cases and 17,642 controls), respectively. The associations of genetic variants with overall and 22 site-specific cancers were extracted from the UK Biobank study (n = 367,561), the FinnGen study (n = 260,405), Biobank Japan (n = 212,453), and international consortia. The associations for one outcome from different data sources were combined by meta-analysis.ResultsIn the European population, the combined odds ratios per 1-unit increase in log odds of genetic liability to RA were 1.06 (95% confidence interval [CI] 1.03-1.10) for head and neck cancer, 1.06 (95% CI 1.02-1.10) for cervical cancer, 0.92 (95% CI 0.87-0.96) for testicular cancer, and 0.94 (95% CI 0.90-0.98) for multiple myeloma. In the East Asian population, the corresponding odds ratios were 1.17 (95% CI 1.06-1.29) for pancreatic cancer, 0.91 (95% CI 0.88-0.94) for breast cancer, and 0.90 (95% CI 0.84-0.96) for ovarian cancer. There were suggestive associations for breast and ovarian cancer and overall cancer in the European population. No other associations were observed.ConclusionThis study suggests that RA may play a role in the development of several site-specific cancers.
| S-EPMC9746148 | biostudies-literature
Project description:Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.
| S-EPMC6885121 | biostudies-literature
Project description:Background:Inflammatory bowel disease (IBD) is commonly divided into 2 entities: Crohn's disease (CD) and ulcerative colitis (UC). Differentiating between these entities when dealing with IBD confined to the colon is important, especially when planning surgical treatment. Due to ambiguous histological or endoscopic findings, accurate diagnosis is not possible in up to 15% of cases. The aim of this study was to determine whether plasma microRNAs (miRNAs) can help differentiate Crohn's colitis (CC) from ulcerative colitis. Methods:Patients with isolated CC and with UC were enrolled in our study from January 2010 to May 2016. Peripheral blood was collected, and total RNA was isolated from plasma. Screening was performed for 380 common miRNAs. miRNAs that were differentially expressed between these 2 groups were chosen, and their differential expression was confirmed using single miRNA assays in a larger sample size. A predictive model was generated using these data. Significantly differentially expressed miRNAs were then validated utilizing the predictive model to assess blinded data from the single assays. Results:Screening was performed on 8 patients from each group. Seven differentially expressed miRNAs were chosen for single assay confirmation. Two miRNAs (miR-598, miR-642) were consistently different between the patient groups (P = 0.013, P = 0.005). Using blinded data, these 2 miRNAs were validated using the predictive model, achieving an overall accuracy of 75% (95% confidence interval, 40.7-92.9). Conclusions:We identified 2 plasma miRNAs that differentiated CC from UC. Our data indicate the promise and feasibility of a plasma miRNA-based assay to distinguish between these 2 conditions.
| S-EPMC5858028 | biostudies-literature
Project description:Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.
| S-EPMC10963262 | biostudies-literature
Project description:Historical records indicate that extensive cultural, commercial and technological interaction occurred between European and Asian populations. What have been the biological consequences of these contacts in terms of gene flow? We systematically estimated gene flow between Eurasian groups using genome-wide polymorphisms from 34 populations representing Europeans, East Asians, and Central/South Asians. We identified recent gene flow between Europeans and Asians in most populations we studied, including East Asians and Northwestern Europeans, which are normally considered to be non-admixed populations. In addition we quantitatively estimated the extent of this gene flow using two statistical approaches, and dated admixture events based on admixture linkage disequilibrium. Our results indicate that most genetic admixtures occurred between 2,400 and 310 years ago and show the admixture proportions to be highly correlated with geographic locations, with the highest admixture proportions observed in Central Asia and the lowest in East Asia and Northwestern Europe. Interestingly, we observed a North-to-South decline of European gene flow in East Asians, suggesting a northern path of European gene flow diffusing into East Asian populations. Our findings contribute to an improved understanding of the history of human migration and the evolutionary mechanisms that have shaped the genetic structure of populations in Eurasia.
| S-EPMC4382708 | biostudies-literature
Project description:BackgroundExcessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn's disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression.ResultsMicroarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva.ConclusionsOur results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.
| S-EPMC4335694 | biostudies-literature
Project description:Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
| S-EPMC6261994 | biostudies-literature
Project description:Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n?=?1,397) and two Chinese Hong Kong sample sets (n?=?3,869 and n?=?785). Through this effort we identified fourteen loci that associated with BMD in East-Asian samples using a false discovery rate (FDR) of 0.05; 1p36 (ZBTB40, P?=?4.3×10(-9)), 1p31 (GPR177, P?=?0.00012), 3p22 (CTNNB1, P?=?0.00013), 4q22 (MEPE, P?=?0.0026), 5q14 (MEF2C, P?=?1.3×10(-5)), 6q25 (ESR1, P?=?0.0011), 7p14 (STARD3NL, P?=?0.00025), 7q21 (FLJ42280, P?=?0.00017), 8q24 (TNFRSF11B, P?=?3.4×10(-5)), 11p15 (SOX6, P?=?0.00033), 11q13 (LRP5, P?=?0.0033), 13q14 (TNFSF11, P?=?7.5×10(-5)), 16q24 (FOXL1, P?=?0.0010) and 17q21 (SOST, P?=?0.015). Our study marks an early effort towards the challenge of cataloguing bone density variants shared by many ethnicities by testing BMD variants that have been established in Europeans, in East-Asians.
| S-EPMC2951352 | biostudies-literature