[Show abstract][Hide abstract] ABSTRACT: Vascular dementia (VD) is the dementia induced by cerebrovascular lesions with a variety of pathophysiological subtypes. Our knowledge of the genetic mechanism of VD was restricted to a few Mendelian forms of VD. The complexity of sporadic VD caused by individual and interactive genetic effects under various environmental exposures renders it difficult to uncover genetic determinants. Much more effort has been made to identify associations of various candidate genes and to explain the variability of the complex VD than the Mendelian VD. The identified genes, however, explain a small portion of the heritability of VD, and the associations are often controversial in different populations. This makes understanding the genetic architecture of VD more complicated. We studied the genes and their sequence variants associated with susceptibility to VD, and many of the genes were involved in lipid metabolism, angiotensin, and inflammation. We also discussed future directions for the association analysis. Endeavors with various approaches would eventually show the genetic architecture of VD and provide a valuable tool in stratifying patients according to their genotypes. This is the first review to introduce a variety of primary studies that may offer some foundation for the genetics of VD.
Full-text · Article · Nov 2010 · Psychiatric genetics
[Show abstract][Hide abstract] ABSTRACT: Simultaneous analysis of multiple genetic variants is an essential strategy for understanding genetic dissection of complex traits, focusing epistasis along with additive and dominance effects of individual genes. Although phenotypic variation for complex traits might be largely explained by epistasis, most analyses have excluded the possibility of epistasis, especially with lack of individual locus effects. The conventional models for estimating all the possible epistatic effects have a decisively vulnerable point of potentially low power or often nonestimable statistics due to a large number of parameters. Restricted partition method (RPM), a recently developed nonparametric approach for estimating epistasis, overcame the drawback but has both biologically and statistically undesirable properties caused by grouping genotypes. A Bayesian method using a Gibbs sampler for estimating epistasis for complex continuous traits was developed to overcome such problems. This method was devised to draw inferences on multilocus genotypic effects by a Bayesian approach based on their marginal posterior distributions and to attain the marginalization of the joint posterior distribution through Gibbs sampler as a Markov chain Monte Carlo. A simulation study revealed that the Bayesian method using a Gibbs sampler was superior to the currently utilized MDR. Especially, prediction errors substantially decreased under various environmental exposures by the Bayesian method using a Gibbs sampler. The programs would be available for both Gamma and Chi-square prior distributions.