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

Abstract

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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Acknowledgements

The study was supported by the Natural Science Foundation of China (81773508, 81673263), the Key Research Project (Social Development Plan) of Jiangsu Province (BE2016667), the Startup Fund from Soochow University (Q413900313, Q413900412), and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Correspondence to Huan Zhang.

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Keywords

  • Blood pressure
  • m6A
  • Methylation
  • Genome-wide association study
  • Gene expression
Fig. 1