Gene Linkage and Systems Biology.

In the past two decades it has become increasingly clear that the risk for many neurodegenerative disorders is at least partially genetic. Assignment of causality for a given gene depends on showing that a particular variant shows either segregation within a family or association with disease across a population. In terms of lifetime risk of disease, the former generally show strong effects compared to the latter. In rare, but interesting, circumstances there are genetic loci that contain different variants that encode either highly penetrant Mendelian disease but also that contribute to risk of sporadic disease. Here, we will discuss the current efforts to complete our understanding of the genetic architecture of neurodegenerative diseases of aging with a particular focus on Parkinson's disease. We will also briefly outline attempts to use systematic approaches to infer relationships between genes associated with the same diseases, which likely demonstrate that in each case there are a relatively small number of underlying biological pathways or processes that may explain pathogenesis.