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An important approach to reducing missing heritability and enhancing success of genome-wide association studies (GWAS) for complex diseases is the identification of traits that are highly heritable and homogeneous in their etiology. Many approaches have been proposed to define such traits based on either cluster analysis or pedigree-based heritable component analysis. None of the existing methods,...
Genetic association analysis of complex diseases has been limited by heterogeneity in their clinical manifestations and genetic etiology. Research has made it possible to differentiate homogeneous subtypes of the disease phenotype. Currently, the most sophisticated subtyping methods perform unsupervised cluster analysis using only clinical features of a disorder, resulting in subtypes for which genetic...
Complex disorders exhibit great heterogeneity in both clinical manifestation and genetic etiology. This heterogeneity substantially limits the identification of geneotype-phenotype associations. Differentiating homogeneous subtypes of a complex phenotype will enable the detection of genetic variants contributing to the effect of subtypes that cannot be detected by the non-differentiated phenotype...
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