scholarly journals A Genome-Wide Association Study Identifying SVEP1 Variant as a Predictor of Response to Tolvaptan for Cirrhotic Ascites

2021 ◽  
Author(s):  
Yasuhito Tanaka ◽  
Hideto Kawaratani ◽  
Hiromi Sawai ◽  
Masaya Onishi ◽  
Tomomi Kogiso ◽  
...  
Keyword(s):  
Association Study ◽  
Failure Probability ◽  
Genome Wide Association Study ◽  
Replication Study ◽  
Genome Wide Association ◽  
Candidate Snps ◽  
Genome Wide ◽  
A Genome ◽  
Study Results ◽  
V2 Receptor

Abstract Background and Aims: Tolvaptan, an orally active vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan’s efficacy for patients with hepatic ascites. Methods: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; > 1.5 kg decrease of BW) were included in the GWAS and replication study. Results: GWAS showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 x 10− 8). Univariate and multivariate analyses showed that blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 1.03, p = 0.02 and OR = 4.24, p < 0.0001, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (= exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. Conclusion: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

scholarly journals A genome-wide association study of antidepressant response in Koreans

2015 ◽  
Vol 5 (9) ◽  
pp. e633-e633 ◽  
Author(s):  
W Myung ◽  
J Kim ◽  
S-W Lim ◽  
S Shim ◽  
H-H Won ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Antidepressant Drugs ◽  
Replication Study ◽  
Genome Wide Association ◽  
Antidepressant Response ◽  
Drug Concentrations ◽  
Genome Wide ◽  
A Genome ◽  
Stage 1

Abstract We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n=711) revealed GWAS significance (P=1.60 × 10-8) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n=870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P=3.57 × 10-8). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20–0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.

scholarly journals Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Srividya Kidambi ◽  
Soumitra Ghosh ◽  
Jane M Kotchen ◽  
Clarence E Grim ◽  
Shanthi Krishnaswami ◽  
...  
Keyword(s):  
Blood Pressure ◽  
African Americans ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide association study of quantitative computed tomographic emphysema in Korean populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sooim Sin ◽  
Hye-Mi Choi ◽  
Jiwon Lim ◽  
Jeeyoung Kim ◽  
So Hyeon Bak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Candidate Snps ◽  
Copd Patients ◽  
Genome Wide ◽  
A Genome ◽  
Novel Snp

AbstractEmphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10–8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10–6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10–6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

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