Genetic regulation of m⁶A RNA methylation and its contribution in human complex diseases

N⁶-methyladenosine (m⁶A) has been established as the most prevalent chemical modification in message RNA (mRNA), playing an essential role in determining the fate of RNA molecules. Dysregulation of m⁶A has been revealed to lead to abnormal physiological conditions and cause various types of human diseases. Recent studies have delineated the genetic regulatory maps for m⁶A methylation by mapping the quantitative trait loci of m⁶A (m⁶A-QTLs), thereby building up the regulatory circuits linking genetic variants, m⁶A, and human complex traits. Here, we review the recent discoveries concerning the genetic regulatory maps of m⁶A, describing the methodological and technical details of m⁶A-QTL identification, and introducing the key findings of the cis- and trans-acting drivers of m⁶A. We further delve into the tissue- and ethnicity-specificity of m⁶A-QTL, the association with other molecular phenotypes in light of genetic regulation, the regulators underlying m⁶A genetics, and importantly, the functional roles of m⁶A in mediating human complex diseases. Lastly, we discuss potential research avenues that can accelerate the translation of m⁶A genetics studies toward the development of therapies for human genetic diseases.