Search for Epistatically Interacting Genetic Variants That Are Associated with Vasovagal Syncope within Biallelic Combinations

Abstract

The most common cause of transient loss of consciousness is vasovagal syncope (VVS), which occurs owing to hypoperfusion of the brain due to the interruption of vegetative blood circulation control leading to arterial hypotension. It is known that there is a genetic predisposition to VVS, but the data on the role of individual genes are quite inconsistent. Using APSampler software, which is based on a Markov chain Monte Carlo technique and Bayesian nonparametric statistics, we identified biallelic combinations associated with VVS and investigated the nature of interaction between their components. We used the previously obtained results of genomic typing of single nucleotide polymorphisms (SNPs) of five genes the products of which are involved in neurohumoral regulation and four SNPs within locus 2q32.1, supplemented with data for new individuals included in the study. The total sample included 175 patients with a confirmed diagnosis of VVS and 200 control individuals without a history of syncope. Eleven pairwise combinations of SNPs of different genes were found to be associated with VVS. Five of these combinations were epistatic, four of which included SNPs at the 2q32.1 locus located within or near noncoding RNA genes. It is suggested that genes of noncoding RNAs localized on chromosome 2 may directly or indirectly (through cascades of interactions) participate in the regulation of the activity of genes forming epistatic combinations with them.