Monogenic Stroke —Can We Overcome Nature With Nurture?

Although genetic underpinnings of several neurological disorders like epilepsy have been described as early as fourth century bce in the Corpus Hippocraticum, discoveries in stroke have been more recent. One of the first reports demonstrating the importance of heredity in stroke pathogenesis occurred in 1974 with the generation of the stroke-prone spontaneously hypertensive rat. This strain was created using selective breeding and has endured as a valuable asset in contemporary stroke research. Nonetheless, half a century later, the precise genetic determinants even in this single, highly specific rodent stroke phenotype have not been completely elucidated despite immense advances in next-generation sequencing and genome mapping. In humans, the role of genetics in stroke is exponentially more complex. Stroke is heterogeneous, as are its predisposing risk factors, which also have their own genetic contributors. Genetics may either mediate or moderate stroke via multiple mechanisms. Genome-wide association studies since 2007 have identified several common loci and variants that typically account for a small proportion of the heritable risk of stroke, stroke subtypes, or conventional stroke risk factors. Monogenic stroke has classically resided on the other end of the continuum, where rare variants in a single gene are often thought to cause diseases. Here, the genetic alteration may contribute to inherited syndromes where stroke is the primary phenotype (eg, cerebral autosomal ...
Source: JAMA Neurology - Category: Neurology Source Type: research