The Genetics of Aneurysms: A Complex Pathophysiology Requiring Complex Analysis

Abstract

formation by developing a genetic risk scale composed of 7 validated SNPs (2, 8). This genetic risk scale was able to demonstrate a stronger association with MCA aneurysms than aneurysms in other locations. This finding represents the first of many needed steps toward using the growing stream of genomic information provided by newer studies. This finding is also consistent with studies on sporadic disease such as meningiomas that have demonstrated a relationship between locality and RNA expression, suggesting that further associations exist but remain unrecognized (3). Future studies must account for phenotypic variability to advance the field toward meaningful clinical applications in aneurysmal therapy. The exclusion of fusiform and irregular aneurysmal morphologies is notable in that this too is likely associated with the biochemistry of aneurysm formation. The primary weakness of the study by van’t Hof et al. (7), the inclusion of a small number of SNPs into the genetic risk scale, should be seen as a call to continue multicenter compilations of genetic data. Differences even between the 2 studied white populations were notable in that multiple SNPs had different associations with MCA location as well as different frequencies of SNP presence within the populations as a whole. Both cohorts were sizable, but it is feasible that the variability in both SNP frequency and demographic characteristics such as familial history (13% in Dutch cohort vs. 39% in Finnish cohort) was secondary to differences in the recruited samples rather than population differences. This variability emphasizes the need for individual and compiled genetic studies if a useful predictive algorithm is to be generated from a comprehensive database of aneurysm-associated genes. Many of the currently known genes associated with aneurysms