scholarly journals A genome‐wide association and replication study of blood pressure in Ugandan early adolescents

2019 ◽  
Vol 7 (10) ◽  
Author(s):  
Swaib A. Lule ◽  
Alexander J. Mentzer ◽  
Benigna Namara ◽  
Allan G. Muwenzi ◽  
Beatrice Nassanga ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Early Adolescents ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

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 for Hypertensive Kidney Disease in Korean Men

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 751
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Integrated Analysis ◽  
Eqtl Analysis ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide ◽  
A Genome

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

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 A Genome-Wide Association Study of Hypertension and Blood Pressure in African Americans

PLoS Genetics ◽  
2009 ◽  
Vol 5 (7) ◽  
pp. e1000564 ◽  
Author(s):  
Adebowale Adeyemo ◽  
Norman Gerry ◽  
Guanjie Chen ◽  
Alan Herbert ◽  
Ayo Doumatey ◽  
...  
Keyword(s):  
Blood Pressure ◽  
African Americans ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1804
Author(s):  
Seong-Beom Cho ◽  
Jinhwa Jang
Keyword(s):  
Blood Pressure ◽  
Association Study ◽  
Genetic Susceptibility ◽  
Genetic Heterogeneity ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Heterogeneity Analysis

Genome-wide association studies have expanded our understanding of the genetic variation of hypertension. Hypertension and blood pressure are influenced by sex-specific differences; therefore, genetic variants may have sex-specific effects on phenotype. To identify the genetic factors influencing the sex-specific differences concerning hypertension, we conducted a heterogeneity analysis of a genome-wide association study (GWAS) on 13,926 samples from a Korean population. Using the Illumina exome chip data of the population, we performed GWASs of the male and female population independently and applied a statistical test that identified heterogeneous effects of the variants between the two groups. To gain information about the biological implication of the genetic heterogeneity, we used gene set enrichment analysis with GWAS catalog and pathway gene sets. The heterogeneity analysis revealed that the rs11066015 of ACAD10 was a significant locus that had sex-specific genetic effects on the development of hypertension. The rs2074356 of HECTD4 also showed significant genetic heterogeneity in systolic blood pressure. The enrichment analysis showed significant results that are consistent with the pathophysiology of hypertension. These results indicate a sex-specific genetic susceptibility to hypertension that should be considered in future genetic studies of hypertension.

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 Rapid response to the Alpha-1 Adrenergic Agent Phenylephrine in the Perioperative Period is Impacted by Genomics and Ancestry

2019 ◽  
Author(s):  
Stephane Wenric ◽  
Janina M. Jeff ◽  
Thomas Joseph ◽  
Muh-Ching Yee ◽  
Gillian M. Belbin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Rapid Response ◽  
Genome Wide Association ◽  
Study Cohort ◽  
Genome Wide Association Studies ◽  
Entire Study ◽  
Entire Cohort ◽  
Genome Wide ◽  
A Genome ◽  
Clinical Covariates

AbstractBackgroundThe emergence of genomic data in biobanks and health systems offers new ways to derive medically important phenotypes, including acute phenotypes that occur during in-patient clinical care. We hypothesized that there is a genetic underpinning to the magnitude of the response to phenylephrine, an α1-adrenergic receptor agonist commonly used to treat hypotension during anesthesia and surgery.MethodsWe quantified the response to phenylephrine by determining the delta between the minimum blood pressure (BP) within five minutes before and the maximum BP within five minutes after bolus administration. We then performed a genome-wide association study (GWAS) adjusted for genetic ancestry, demographics, and relevant clinical covariates to investigate genetic factors underlying individual differences systolic BP response to phenylephrine (ΔSBP), as well as mean arterial pressure (ΔMAP) and diastolic BP (ΔDBP), for both the entire study cohort as well as for each of 3 ancestry sub-cohorts; European American(EA), African American(AA), and Hispanic American(HA).Results4,317 patients met inclusion criteria, of which 3,699 were genotyped. Average ΔBP values over the entire cohort were ΔSBP=17(+-25) mmHg, ΔMAP=14(+-18) mmHg, ΔDBP=11(+-14) mmHg. The largest difference between populations was observed for ΔSBP (ΔSBPEA=20(+-24) mmHg; ΔSBPHA=16(+-25) mmHg; ΔSBPAA=15(+-25) mmHg). The differences remained after adjusting for clinical covariates and ancestry (EA vs. HA: ΔSBP, p<0.032;ΔMAP, p<0.021;ΔDBP,p<0.008);(EA vs. AA:ΔSBP,p<5.13×10-5;ΔMAP,p<2.1×10-4;ΔDBP,p<3.3×10-4). GWAS revealed significant associations between loci and BP response in 5 different genome regions (p<5×10-8) in the entire cohort, and suggestive associations in 2 different regions in EAs (p<6×10-8,p<7×10-8). We observed non-random enrichment in association with SBP drug response in 165 loci previously reported to be associated with systolic blood pressure. Finally, we discovered rare variants, rs188427942 and rs147664194 present at ∼1% in EAs and rs146535276 present at ∼1% in AAs respectively, where patients carrying one copy of these variants show no response to phenylephrine.ConclusionsIt is possible to derive a quantitative phenotype suited for comparative statistics and genome-wide association studies from routinely collected perioperative data. There are population differences in rapid response to phenylephrine, large effect alleles and novel genes affecting pharmaceutical response, and phenylephrine non-responders, with implications for personalized treatment during surgery.

scholarly journals A genome-wide association study of childhood adiposity and blood lipids

2021 ◽  
Vol 6 ◽  
pp. 303
Author(s):  
Katie O'Nunain ◽  
Eleanor Sanderson ◽  
Michael Holmes ◽  
George Davey Smith ◽  
Tom Richardson
Keyword(s):  
Blood Pressure ◽  
Genetic Correlations ◽  
Later Life ◽  
Functional Enrichment ◽  
Genome Wide Association ◽  
Health Concern ◽  
Genome Wide Association Studies ◽  
Childhood Adiposity ◽  
Genome Wide ◽  
A Genome

Background: The rising prevalence of childhood obesity and dyslipidaemia is a major public health concern due to its association with morbidity and mortality in later life. Methods: In this study, we have conducted genome-wide association studies (GWAS) for eight measures of adiposity and lipids in a cohort of young individuals (mean age 9.9) from the Avon Longitudinal Study of Parents and Children (ALSPAC). These measures were body mass index (BMI), systolic and diastolic blood pressure, high- density and low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I and apolipoprotein B. We next undertook functional enrichment, pathway analyses and linkage disequilibrium (LD) score regression to evaluate genetic correlations with later-life cardiometabolic diseases. Results: Using GWAS we identified 14 unique loci associated with at least one risk factor in this cohort of age 10 individuals (P<5x10-8), with lipoprotein lipid-associated loci being enriched for liver tissue-derived gene expression and lipid synthesis pathways. LD score regression provided evidence of various genetic correlations, such as childhood systolic blood pressure being genetically correlated with later-life coronary artery disease (rG=0.26, 95% CI=0.07 to 0.46, P=0.009) and hypertension (rG=0.37, 95% CI=0.19 to 0.55, P=6.57x10-5), as well as childhood BMI with type 2 diabetes (rG=0.35, 95% CI=0.18 to 0.51, P=3.28x10-5). Conclusions: Our findings suggest that there are genetic variants inherited at birth which begin to exert their effects on cardiometabolic risk factors as early as age 10 in the life course. However, further research is required to assess whether the genetic correlations we have identified are due to direct or indirect effects of childhood adiposity and lipid traits.

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