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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.

Original publication

DOI

10.1111/jch.14552

Type

Journal article

Journal

J Clin Hypertens (Greenwich)

Publication Date

10/2022

Volume

24

Pages

1370 - 1380

Keywords

blood pressure, genetic variation, genome-wide association study, polymorphism, single nucleotide, Humans, Male, Blood Pressure, Genome-Wide Association Study, Hypertension, Biological Specimen Banks, United Kingdom