Search for epistatically interacting genetic variants that are associated with vasovagal syncope within biallelic combinations

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Abstract

The most common cause of transient loss of consciousness is vasovagal syncope (VVS), which occurs due 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 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 5 genes, the products of which are involved in neurohumoral regulation, and 4 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.

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About the authors

B. V. Titov

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Email: olga.favorova@gmail.com
Russian Federation, Moscow, 121552; Moscow, 117997

N. F. Matveeva

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Email: olga.favorova@gmail.com
Russian Federation, Moscow, 121552; Moscow, 117997

E. A. Bazyleva

Chazov National Medical Research Center of Cardiology

Email: olga.favorova@gmail.com
Russian Federation, Moscow, 121552

A. V. Pevzner

Chazov National Medical Research Center of Cardiology

Email: olga.favorova@gmail.com
Russian Federation, Moscow, 121552

O. O. Favorova

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Author for correspondence.
Email: olga.favorova@gmail.com
Russian Federation, Moscow, 121552; Moscow, 117997

References

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Supplementary files

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2. Fig. 1. Schematic representation of biallelic combinations of polymorphic regions of various genes associated with VBO. Each combination is depicted as a pair of SNPs as rectangles connected by orange lines; triple lines connect the components of epistatic combinations, single lines are the components of combinations, epistasis between which is not detected. An asterisk near the line means that the combination is described in [11]. The yellow rectangles are SNPs in genes whose products are involved in neurohumoral regulation (group 1), the blue ones are SNPs located on chromosome 2 at locus 2q32.1 (group 2). In the green frame – the SNP, whose association with the BBO was shown only as part of combinations, in the blue frame – also alone.

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