• Eun Pyo Hong, Bong Jun Kim, Dong Hyuk Youn, Jae Jun Lee, Hong Jun Jeon, Hyuk Jai Choi, Yong Jun Cho, Jin Pyeong Jeon, and First Korean Stroke Genetics Association Research (The FirstKSGAR) Study.
• Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Republic of Korea.
• World Neurosurg. 2022 Oct 1; 166: e109e117e109-e117.

ObjectiveCompared to European, Japanese, and Chinese populations, genetic studies on intracranial aneurysms (IAs) in Koreans are lacking. We conducted an updated genome-wide association study (GWAS) to more accurately identify candidate variations predicting IA by genotype correction and imputation than in the first Korean GWAS.MethodsWe performed a high-throughput imputation of single-nucleotide polymorphisms (SNPs) and genotype missing values for 250 IA and 296 controls. Out of a total of 7,333,746 sites with an imputation R2 score of ≥0.5, 6,105,212 SNPs were analyzed. A high-throughput GWAS was performed after adjusting for clinical variables and 4 principal component analysis values.ResultsA total of 39 SNPs reached a significant genome-wide threshold (P < 5 × 10-8). After pruning by pairwise linkage disequilibrium (r2 < 0.8), 11 SNPs were consistently associated with IA. Six tagging SNPs, including rs3120004, rs1851347, rs1522095, rs7779989, rs12935558, rs3826442, and rs2440154, showed strong linkage disequilibrium tower tagging haplotype structures. Among them, rs3120004 tagged a large and strong haplotype structure between LOC440704 and RGS18 genes in 1q31.2 (odds ratio, 2.34; 95% confidence interval, 1.74-3.14; P = 1.4 × 10-8). The rs2440154 (SLC47A1, 17p11.2) SNP increased the risk of IA most significantly (odds ratio, 2.90; 95% confidence interval, 2.07-4.08; P = 8.2 × 10-10). The region encompassing rs3826442 (MYH13, 17p13.1) showed a high recombination rate of approximately 70 cM/Mbp.ConclusionsOur updated GWAS using high-throughput imputation approaches can be an informative milestone in understanding IA formation via susceptibility loci in this stage before large-scale genome-wide association meta-analysis.Copyright © 2022 Elsevier Inc. All rights reserved.

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