Unbiased genome-wide approaches to identify vulnerability factors in Huntington's disease

Since the discovery of mutations in the huntingtin (HTT) gene as being the cause of Huntington's disease (HD), numerous unbiased genome-wide screens have been undertaken in all major model systems to identify genetic modulators of mutant HTT aggregation and toxicity. These screening efforts have yielded invaluable mechanistic insights that have complemented and, in some cases, initiated new lines of hypothesis-driven research. Here we review these screens and discuss future directions that may uncover new disease mechanisms and therapeutic targets.