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

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.

Download Full-text

A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Genes ◽

10.3390/genes12050751 ◽

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.

Download Full-text

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

PLoS Genetics ◽

10.1371/journal.pgen.1000564 ◽

2009 ◽

Vol 5 (7) ◽

pp. e1000564 ◽

Cited By ~ 268

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

Download Full-text

Genome-Wide Association Study of Postoperative Cognitive Dysfunction in Older Surgical Patients

10.21203/rs.3.rs-40268/v1 ◽

2020 ◽

Author(s):

Marc Rickenbacher ◽

Céline S Reinbold ◽

Stefan Herms ◽

Per Hoffmann ◽

Sven Cichon ◽

...

Keyword(s):

Association Study ◽

Candidate Genes ◽

Cognitive Dysfunction ◽

Genome Wide Association Study ◽

Postoperative Cognitive Dysfunction ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Genome Wide Association ◽

Genome Wide ◽

A Genome

Abstract Background: Postoperative cognitive dysfunction (POCD) is a common neurocognitive complication after surgery and anesthesia, particularly in elderly patients. Various studies have suggested genetic risk factors for POCD. The study aimed to detect genome-wide associations of POCD in older patients.Methods: In this prospective observational cohort study, participants aged ≥65 years completed a set of neuropsychological tests before, at 1 week, and 3 months after major noncardiac surgery. Test variables were converted into standard scores (z-scores) based on demographic characteristics. POCD was diagnosed if the decline was >1 standard deviation in ≥2 of the 15 variables in the assessment battery. A genome-wide association study (GWAS) was performed to determine potential alleles that are linked to the POCD phenotype. In addition, candidate genes for POCD were identified in a literature search for further analysis.Results: Sixty-three patients with blood samples were included in the study. POCD was diagnosed in 47.6% of patients at 1 week and in 34.2% of patients at 3 months after surgery. Insufficient sample quality led to exclusion of 26 patients. In the remaining 37 patients, a GWAS was performed, but no association (P < 5*10-8) with POCD was found. The subsequent gene set enrichment analysis of 34 candidate genes did not reveal any significant associations.Conclusion: In this patient cohort, a GWAS did not reveal an association between specific genetic alleles and POCD at 1 week and 3 months after surgery. Future genetic analysis should focus on specific candidate genes for POCD.Trial registration: ClinicalTrials.gov (NCT02864173)

Download Full-text