Detection of M⁶A-associated SNPs as Potential Functional Variants for Coronary Artery Disease

Abstract

Aim: To investigate the effects of m⁶A-single nucleotide polymorphisms (SNPs) on coronary artery disease (CAD). Methods: We examined the association of m⁶A-SNPs with CAD in about 185,000 cases and controls and further performed eQTL and differential expression analyses to support the identified m⁶A-SNPs. Results: Among the 4390 m⁶A-SNPs detected, 304 seemed to be associated with CAD (p < 0.05). SNP rs12286 was significantly associated with CAD at genome-wide level (p = 4.5 × 10⁻⁹). rs12286 was predicted to influence m⁶A methylation and have the potential to alter regulatory motifs binding, which may in turn regulate the expression of ADAMTS7 (p = 1.26 × 10⁻⁸). Conclusion: The present study found plenty of CAD-associated m⁶A-SNPs and demonstrated the potential functionality of the identified SNPs.

Keywords::

• ADAMTS7
• coronary artery disease
• eQTL
• FTO
• gene expression
• genome-wide association study
• m⁶A
• multifunctional variants
• single nucleotide polymorphism
• transcription regulation

Supplementary Material

Financial&competing interests disclosure

The study was supported by Natural Science Foundation of China (grant number. 81773508), the Key Research Project (Social Development Plan) of Jiangsu Province (grant number. BE2016667), the Startup Fund from Soochow University (grant numbers Q413900313, Q413900412), the Project funded by the China Postdoctoral Science Foundation (gant numbers 2013M530269 and 2014M551649, 2014T70547) and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The study was supported by Natural Science Foundation of China (grant number. 81773508), the Key Research Project (Social Development Plan) of Jiangsu Province (grant number. BE2016667), the Startup Fund from Soochow University (grant numbers Q413900313, Q413900412), the Project funded by the China Postdoctoral Science Foundation (gant numbers 2013M530269 and 2014M551649, 2014T70547) and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.