Gene-gene Interaction Analyses for Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27–1.65, P = 4.3 × 10–8). Eight additional gene-gene interactions were also marginally significant (P < 5 × 10–7). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.

The Genetic Puzzle of Familial Atrial Fibrillation

“…In 2016, Lin and his colleagues investigated if gene-gene interaction would affect AF susceptibility. However, this study could not find any significant association and a larger cohort containing participants from other ethnic groups is indeed justified (115).…”

Effect of sex hormone–binding globulin polymorphisms on the outcome of in vitro fertilization‐embryo transfer for polycystic ovary syndrome patients: A case‐control study

“…21 In addition to evaluating the effects of individual SNPs, recent studies also considers the potential combined effects and SNP-SNP interactions in two or more loci. [22][23][24] Therefore, we analyzed not only the individual effects of SNP, but also the combined effects of SNPs and SNP-SNP interactions in SHBG to access their potential effects on PCOS. The rs6259 and rs727428 genotypes did not exhibit any significant differences in the PCOS subtypes, however, the haplotype analysis of SHBG rs6259 and rs727428 in the PCOS and control groups revealed that AC, AT, GC, and GT were the common haplotypes and the frequency distribution of AC, AT, GC, and GT was statistically significant.…”

Inferior Colliculus Transcriptome After Status Epilepticus in the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal

“…The two families of nucleoside transporters SLC28 and SLC29 have several members that participates in modulating neurotransmission, vascular tone, immune responses and other physiological processes (Mulinta et al, 2017). The Slc28a1 gene stands out as the protein-coding gene for Solute Carrier Family 28 Member 1 (Pastor-Anglada et al, 2005), and has been related to some pathologies such as cancer (Wang and Buolamwini, 2019), atrial fibrillation (Lin et al, 2016), and antiretroviral therapy absorption (Moketla et al, 2018), but not to epilepsy. Thus, Slc28a1 overexpression in the IC of GASH/Sal animals in comparison with their controls may result from a process of physiological compensation whereby Slc28a1 overexpression increases nucleic acid synthesis toward activating molecular processes to attenuate cellular stress, and consequently, contributing to epileptogenesis in the GASH/Sal.…”