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Meta-Analysis
. 2015 Aug;46(8):2299-301.
doi: 10.1161/STROKEAHA.115.009838. Epub 2015 Jun 25.

Rare Coding Variation and Risk of Intracerebral Hemorrhage

Farid Radmanesh  1 , Guido J Falcone  1 , Christopher D Anderson  1 , David McWilliams  1 , William J Devan  1 , W Mark Brown  1 , Thomas W K Battey  1 , Alison M Ayres  1 , Miriam R Raffeld  1 , Kristin Schwab  1 , Guangyun Sun  1 , Ranjan Deka  1 , Anand Viswanathan  1 , Joshua N Goldstein  1 , Steven M Greenberg  1 , David L Tirschwell  1 , Scott L Silliman  1 , Magdy Selim  1 , James F Meschia  1 , Devin L Brown  1 , Bradford B Worrall  1 , Carl D Langefeld  1 , Daniel Woo  1 , Jonathan Rosand  2
Affiliations
Meta-Analysis

Rare Coding Variation and Risk of Intracerebral Hemorrhage

Farid Radmanesh et al. Stroke. 2015 Aug.

Abstract

Background and purpose: Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage.

Methods: A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed.

Results: No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing.

Conclusions: Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.

Keywords: apolipoproteins E; cerebral hemorrhage; genome-wide association study.

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Figures

Figure 1
Figure 1
Forest plot depicting effect estimates for rs769449
Figure 2
Figure 2
Regional association plot for 19q13 locus
See this image and copyright information in PMC

References

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