Examination of the associations between m⁶A-associated single-nucleotide polymorphisms and blood pressure.

N⁶-methyladenosine (m⁶A) has been shown to play critical roles in many biological processes and a variety of diseases. The aim of this study was to investigate the association between m⁶A-associated single-nucleotide polymorphisms (m⁶A-SNPs) and blood pressure (BP) in large-scale genome-wide association studies and to test whether m⁶A-SNPs are enriched among the SNPs that were associated with BP. Furthermore, gene expression analysis was performed to obtain additional evidence for the identified m⁶A-SNPs. We found 1236 m⁶A-SNPs that were nominally associated with BP, and 33 of them were significant genome wide. The proportion of m⁶A-SNPs with a P < 0.05 was significantly higher than that of non-m⁶A-SNPs. Using fgwas, we found that SNPs associated with diastolic BP (P < 5 × 10^-8) were significantly enriched with m⁶A-SNPs (log 2 enrichment of 2.67, 95% confidence interval: [0.42, 3.68]). Approximately 10% of the BP-associated m⁶A SNPs were associated with coronary artery disease or stroke. Most of these m⁶A-SNPs were strongly associated with gene expression. We showed that rs56001051, rs9847953, rs197922, and rs740406 were associated with C1orf167 (P = 0.019), ZNF589 (P = 0.013), GOSR2 (P = 0.001), and DOT1L (P = 0.032) expression levels in peripheral blood mononuclear cells of 40 Chinese individuals, respectively. The present study identified many BP-associated m⁶A-SNPs and demonstrated their potential functionality. The results suggested that m⁶A might play important roles in BP regulation.

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