Hong Eun Pyo, Youn Dong Hyuk, Kim Bong Jun, Lee Jae Jun, Nam Sehyeon, Yoo Hyojong, Kim Heung Cheol, Rhim Jong Kook, Park Jeong Jin, Jeon Jin Pyeong
Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea.
Department of Materials Science and Chemical Engineering, Hanyang University, Ansan, Korea.
J Korean Neurosurg Soc. 2023 Jul;66(4):409-417. doi: 10.3340/jkns.2022.0026. Epub 2022 Oct 24.
The association between boule (BOLL) and endothelin receptor type A (EDNRA) loci and intracranial aneurysm (IA) formation has been reported via genome-wide association studies. We sought to identify genome-wide interactions involving BOLL and EDNRA loci for IA in a Korean adult cohort.
Genome-wide pairwise interaction analyses of BOLL and EDNRA involving 250 patients with IA and 296 controls were performed using the additive effect model after adjusting for confounding factors.
Among 512575 single-nucleotide polymorphisms (SNPs), 23 and 11 common SNPs suggested a genome-wide interaction threshold (p<1.25×10-8) involving rs700651 (BOLL) and rs6841581 (EDNRA). Rather than singe SNP effect of BOLL or EDNRA on IA development, they showed a synergistic effect on IA formation via multifactorial pair-wise interactions. The rs1105980 of PTCH1 gene showed the most significant interaction with rs700651 (natural log-transformed odds ratio [lnOR], 1.53; p=6.41×10-11). The rs74585958 of RYK gene interacted strongly with rs6841581 (lnOR, -19.91; p=1.64×10-9). Although, there was no direct interaction between BOLL and EDNRA variants, two EDNRA-interacting gene variants of TNIK (rs11925024 and rs1231) and FTO (rs9302654), and one BOLL-interacting METTL4 gene variant (rs549315) exhibited marginal interaction with BOLL gene.
BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.
通过全基因组关联研究报道了布尔基因（BOLL）和A型内皮素受体（EDNRA）基因座与颅内动脉瘤（IA）形成之间的关联。我们试图在韩国成年队列中确定涉及BOLL和EDNRA基因座与IA的全基因组相互作用。
在调整混杂因素后，使用加性效应模型对250例IA患者和296例对照进行BOLL和EDNRA的全基因组成对相互作用分析。
在512575个单核苷酸多态性（SNP）中，23个和11个常见SNP表明涉及rs700651（BOLL）和rs6841581（EDNRA）的全基因组相互作用阈值（p<1.25×10-8）。它们并非通过BOLL或EDNRA对IA发展的单一SNP效应，而是通过多因素成对相互作用对IA形成表现出协同效应。PTCH1基因的rs1105980与rs700651表现出最显著的相互作用（自然对数转换优势比[lnOR]，1.53；p=6.41×10-11）。RYK基因的rs74585958与rs6841581强烈相互作用（lnOR，-19.91；p=1.64×10-9）。虽然BOLL和EDNRA变体之间没有直接相互作用，但TNIK（rs11925024和rs1231）和FTO（rs9302654）的两个与EDNRA相互作用的基因变体，以及一个与BOLL相互作用的METTL4基因变体（rs549315）与BOLL基因表现出边缘相互作用。
BOLL或EDNRA可能通过多因素成对相互作用对IA形成产生协同效应。
