The genetic architecture of blood pressure variability: A genome‐wide association study of 9370 participants from UK Biobank

Autor: Pingping Jia, Na Zhan, Baker K. K. Bat, Qi Feng, Kelvin K. F. Tsoi
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Clinical Hypertension, Vol 24, Iss 10, Pp 1370-1380 (2022)
Druh dokumentu: article
ISSN: 1751-7176
1524-6175
DOI: 10.1111/jch.14552
Popis: Abstract Long‐term blood pressure variability (BPV) is a risk factor for cardiovascular diseases, dementia, and stroke. However, its genetic architecture is not fully understood. This study aims to explore its genetic factors and provide more evidence on the mechanisms and further pathological study of BPV. The genome‐wide association study (GWAS) is based on the UK Biobank cohort. There were four data collection rounds from 2006 to 2020, and 9370 participants with more than three blood pressure measurements were included. They had a median age of 55 and a male percentage of 50.1%. The phenotypes (BPV) were calculated by four methods and the genetic data contains 6 884 260 single nucleotide polymorphisms (SNPs) after imputation and quality control. A linear regression model was performed with adjustments for sex, age, genotype array, and a significant principal component. Subgroup analysis was performed on hypertension‐free participants. The significant and suggestive significant P thresholds were set as 5 × 10−8 and 1 × 10−6. Six genetic loci (BAD, CCDC88B, GPR137, PLCB3, RPS6KA4 for systolic BPV, and WWC2 for diastolic BPV) were identified by coding region SNPs at the suggestive significant P threshold (1 × 10−6). Among them, gene CCDC88B and RPS6KA4 reached the significant P threshold (5 × 10−8), with the strongest signal of SNP rs1229536170 (P = 6.36 × 10−8, β = –.29). The annotation results indicate that genes CCDC88B, GPR137, RPS6KA4, and BAD are associated with long‐term SBPV. Their functions of inflammation, epithelial dysfunction, and apoptosis are related to artery stiffness, which was reported as potential mechanisms of BPV.
Databáze: Directory of Open Access Journals
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