Jose Gutierrez, MD, MPH
Devan WJ, Falcone GJ, Anderson CD, Jagiella JM, Schmidt H, Hansen BM, et al. HeritabilityEstimates Identify a Substantial Genetic Contribution to Risk and Outcome ofIntracerebral Hemorrhage. Stroke. 2013
When we think of intracranial hemorrhage (ICH), we often think that deep-seated ICH tends to be caused by hypertension and that lobar ICH is suggestive of cerebral amyloid angiopathy. But, many other unknown factors might influence the risk to develop ICH. In this paper, Devan et al. obtained genome-wide genotype data for 791 ICH cases and 876 controls looking to quantify the heritability of ICH risk, ICH initial volume and 90-day mortality. The author stratified the ICH in deep vs. lobar hemorrhage to evaluate the heritability of each ICH subtype. To further evaluate for confounding effects of known risk factors for these hemorrhage subtypes, the authors suppressed genes associated with ICH lobar volume (complement component receptor 1) and those associated with hypertension.
They found a high heritability to ICH. Approximately 44% of ICH variance was accounted for by genetic differences between cases vs. groups; a higher proportion of the variance was attributable to non-APOE loci than to APOE loci. After stratifying by location (deep vs. lobar hemorrhage), non-APOE loci contributed to the variance seen in both types of ICH while APOE locus only contributed to lobar ICH. Suppressing the complement component receptor 1 did change minimally the total heritability of lobar and total ICH and suppressing loci associated with hypertension changed minimally the total and deep ICH. The results were less robust for volume and 90-day mortality. Only APOE focus was significantly associated with lobar ICH volume but not with deep or total ICH volumes. For 90-day mortality, 41% of heritability was found for non-APOE loci and 1 for APOE gene, both were not significant.
The results suggest that many other unknown factors might influence the risk of ICH. Understanding these factors may change our understanding of ICH pathophysiology and help us identify new ways to prevent and treat this devastating disease.