P3718Identification of nine genes as novel susceptibility loci for early-onset ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage
| Autor: | Jun Sakuma, Y Yamase, Ichiro Takeuchi, Hideki Horibe, Takeshi Hibino, Katsuhiko Kato, Tetsuo Fujimaki, Toyoaki Murohara, Yoshiji Yamada, Taizo Kondo, I Yasukochi, Mitsutoshi Oguri |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | European Heart Journal. 40 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/eurheartj/ehz745.0572 |
| Popis: | Background Given that substantial genetic components have been shown in ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), a heritability may be higher in early-onset than late-onset individuals with these conditions. Although genome-wide association studies have identified various genes and loci significantly associated with ischemic stroke, ICH, or intracranial aneurysm mainly in European ancestry populations, genetic variants that contribute to susceptibility to these disorders in Japanese individuals remain to be identified definitively. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to ischemic stroke, ICH, or SAH in Japanese. We have now performed exome-wide association studies (EWASs) in early-onset subjects with these conditions and corresponding controls. Methods A total of 6649 individuals aged ≤65 years were examined. For the EWAS of ischemic or hemorrhagic stroke, 6224 individuals (450 subjects with ischemic stroke, 5774 controls) or 6179 individuals (261 subjects with ICH, 176 subjects with SAH, 5742 controls), respectively, were examined. EWASs were performed with the use of Illumina Human Exome-12 v1.2 DNA Analysis BeadChip or Infinium Exome-24 v1.0 BeadChip. To compensate for multiple comparisons of allele frequencies with ischemic stroke, ICH, or SAH, we applied a false discovery rate (FDR) of Results The relation of allele frequencies of 31,245 single nucleotide polymorphisms (SNPs) that passed quality control to ischemic stroke was examined with Fisher's exact test, and 31 SNPs were significantly (FDR Conclusion We have thus newly identified nine genes that confer susceptibility to early-onset ischemic stroke, ICH, or SAH. Determination of genotypes for the SNPs in these genes may prove informative for assessment of the genetic risk for ischemic stroke, ICH, or SAH in Japanese. |
| Databáze: | OpenAIRE |
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