On the other side of the equation (from studying genetic architecture of schizophrenia as a multifactorial trait), this paper [attached] describes the importance or relevance of attempting to subdivide the broad spectrum of parkinsonian disorders (i.e. defining phenotypic architecture of a complex disease). A better definition of the trait … should help in focusing on genotype-phenotype associations more crisply or more robustly.
Herein, authors prioritize, as multi-system Lewy body disease (MLBD), those genetic forms of Parkinson disease that point the way toward a mechanistic understanding of the majority of sporadic disease within the Parkinsonian spectrum. Pathological diagnosis of genetic subtypes offers the prospect of distinguishing different mechanistic trajectories with a common mutational etiology, differing outcomes from varying allelic bases, and those disease-associated variants that can be used in gene-environment analysis.
By clearly delineating parkinsonian disorders into subclasses on the basis of molecular mechanisms with well-characterized outcome expectations––should be helpful as the basis for refining these forms of neurodegeneration as research substrate––through the use of cell models derived from affected individuals, … while ensuring that clinically collected data can be used for therapeutic decisions and research, without increasing the noise and confusion engendered by the collection of data against a range of historically defined criteria. Nat Genet Dec 2o15; 47: 1378–1384