Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Novel Genome-Wide Interactions Mediated via BOLL and EDNRA Polymorphisms in Intracranial Aneurysm

  • Eun Pyo Hong (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Dong Hyuk Youn (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Bong Jun Kim (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Jae Jun Lee (Institute of New Frontier Research, Hallym University College of Medicine) ;
  • Sehyeon Nam (Department of Materials Science and Chemical Engineering, Hanyang University) ;
  • Hyojong Yoo (Department of Materials Science and Chemical Engineering, Hanyang University) ;
  • Heung Cheol Kim (Department of Radiology, Hallym University College of Medicine) ;
  • Jong Kook Rhim (Department of Neurosurgery, Jeju National University College of Medicine) ;
  • Jeong Jin Park (Department of Neurology, Konkuk University Medical Center) ;
  • Jin Pyeong Jeon (Department of Neurosurgery, Hallym University College of Medicine)
  • Received : 2022.02.08
  • Accepted : 2022.10.20
  • Published : 2023.07.01
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Abstract

Objective : 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. Methods : 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. Results : 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. Conclusion : BOLL or EDNRA may have a synergistic effect on IA formation via multifactorial pair-wise interactions.

Keywords

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HR21C0198) and Hallym University Research Fund. All genotype and phenotype resources are managed by "The First Korean Stroke Genetics Association Research" study constructed from the participating hospital stroke database.

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