Rare Coding Variation And Risk Of Intracerebral Hemorrhage

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 19 q13 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.