anxiety comprises many clinical descriptions and phenotypes. a genetic predisposition to anxiety is undoubted; however, the nature and extent of that contribution is still unclear. extensive genetic studies of the serotonin (5-hydroxytryptamine, 5-ht) transporter (5-htt) gene have revealed how variation in gene expression can be correlated with anxiety phenotypes. complete genome-wide linkage s...

The principal component method and the mixed effects model represent two popular approaches to controlling for population structure and cryptic relatedness in genetic association studies. There are only a handful of studies comparing their performance. These studies are typically based on simulation studies and the results are therefore limited in their applicability. In this paper, we conduct ...

Mutual information (MI) is a robust nonparametric statistical approach for identifying associations between genotypes and gene expression levels. Using the data of Problem 1 provided for the Genetic Analysis Workshop 15, we first compared a quantitative MI (Tsalenko et al. 2006 J Bioinform Comput Biol 4:259-4) with the standard analysis of variance (ANOVA) and the nonparametric Kruskal-Wallis (...

When estimating the power of genetic association studies, the allele and genotype frequencies are often assumed to be known, and the numbers of individuals with each genotype are set equal to their expectations under Hardy-Weinberg equilibrium. In fact, both allele and genotype frequencies are unknown and thus random. It has previously been suggested that ignoring uncertainty in these parameter...

The purpose of this review is to focus on the three most important themes in genetic association studies using randomly selected patients (case, affected) and normal samples (control, unaffected), so that students and researchers alike who are new to this field may quickly grasp the key issues and command basic analysis methods. These three themes are: elementary categorical analysis; disease m...

In genetic association studies, investigators compare allele or genotype frequencies in unrelated case and control subjects or examine preferential allele transmissions from parents to affected offspring. In many genetic case-control studies, the collection of DNA material extends to relatives such as parents of cases. Thus, case-control and case-parent trio association analyses are possible. W...

In recent years, progress has been made in the identification of causative factors in most single gene disorders and those with genes of major effect. In comparison, no genes contributing to a complex disorder have been unambiguously identified. A number of reasons for this have been previously presented in theoretical papers. Alcoholism is such a complex illness and genetic studies into its un...

This paper proposes a semiparametric methodology for modeling multivariate and conditional distributions. We first build a multivariate distribution whose dependence structure is induced by a Gaussian copula and whose marginal distributions are estimated nonparametrically via mixtures of B-spline densities. The conditional distribution of a given variable is obtained in closed form from this mu...

Most studies on consanguinity have been conducted on contemporary populations and have focused on the prevalence and types of preferred intra-familial marriage. With its comprehensive birth, marriage and deaths records dating back to the late 17th century, and the legal bar on first cousin marriage removed in the mid-19th century, Sweden offers unique opportunities to examine the factors that d...