Rare Coding Variation and Risk of Intracerebral Hemorrhage

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


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / epidemiology
  • Cerebral Hemorrhage / genetics*
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics*
  • Genome-Wide Association Study / methods*
  • Humans
  • Male
  • Middle Aged
  • Risk Factors