Exome-chip association analysis of intracranial aneurysms
OBJECTIVETo investigate to what extent low-frequency genetic variants (with minor allele frequencies 5 and >0 to test the hypothesis that multiple variants within the same gene are associated with IA risk. Significant results were tested in a replication cohort of 425 patients with IA and 311 con...
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Veröffentlicht in: | Neurology 2020-02, Vol.94 (5), p.e481-e488 |
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Sprache: | eng |
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Zusammenfassung: | OBJECTIVETo investigate to what extent low-frequency genetic variants (with minor allele frequencies 5 and >0 to test the hypothesis that multiple variants within the same gene are associated with IA risk. Significant results were tested in a replication cohort of 425 patients with IA and 311 controls, and results of the 2 cohorts were combined in a meta-analysis.
RESULTSAfter QC, 995 patients with IA and 2,080 controls remained for further analysis. The single variant analysis comprising 46,534 SNVs did not identify significant loci at the genome-wide level. The gene-based tests showed a statistically significant association for fibulin 2 (FBLN2) (best p = 1 × 10 for the VT test, MAC >5). Associations were not statistically significant in the independent but smaller replication cohort (p > 0.57) but became slightly stronger in a meta-analysis of the 2 cohorts (best p = 4.8 × 10 for the SKAT, MAC ≥1).
CONCLUSIONGene-based tests indicated an association for FBLN2, a gene encoding an extracellular matrix protein implicated in vascular wall remodeling, but independent validation in larger cohorts is warranted. We did not identify any significant associations for single low-frequency genetic variants. |
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ISSN: | 0028-3878 1526-632X |
DOI: | 10.1212/WNL.0000000000008665 |