Editorial comment--Unraveling the pagodian architecture of stroke as a complex disorder.

Abstract

The last decade has witnessed an explosion of hospital-based association studies aimed at deciphering the genetic architecture of complex disorders. Most of these studies attempt such major undertakings without taking into consideration the phenotypic heterogeneity of these disorders. The population-based meta-analyses presented by Schulz and colleagues1 in this issue of Stroke brings home a very significant point: a complex disorder is not a uniform entity, but a composite of several elemental pathologies affecting particular organ system(s). Most genetic association studies on stroke, for example, pool its various subtypes, amalgamate several ethnicities for the sake of increasing sample size, and genotype only one or a few polymorphisms within candidate genes. In their endeavor to associate a single biallelic polymorphism with a complex disorder, such studies overlook the Factor(s) X which mediate the pathology. In essence, such an association is a jump across the Atlantic. The result is that the literature is flooded with a large number of published papers with extensive heterogeneity and publication bias. Sporadic stroke, as are most complex disorders, is heterogeneous. It can be divided into two major categories, hemorrhagic and ischemic stroke, each having several subcategories which can be identified as distinct phenotypes with their own etiologies. In spite of the recognition of these concepts for a long time, Schulz …