In the first article of this series, we reviewed the basic genetics concepts necessary to understand genetic association studies. In this second article, we enumerate the major issues in judging the validity of these studies, framed as critical appraisal questions. Was the disease phenotype properly defined and accurately recorded by someone blind to the genetic information? Have any potential ...

The explosion of genetic information over the last decade presents an analytical challenge for genetic association studies. As the number of genetic variables examined per individual increases, both variable selection and statistical modeling tasks must be performed during analysis. While these tasks could be performed separately, coupling them is necessary to select meaningful variables that e...

Published genetic association studies have produced controversial results regarding the association of SELE gene polymorphisms (A516C and G98T) and CAD susceptibility. We therefore chose to perform a meta-analysis to determine the association.Twenty-seven eligible articles were identified through electronic databases, providing 5170 CAD cases and 4996 controls. Fixed-effects or random-effects s...

BACKGROUND Numerous epidemiological studies have evaluated the associations between ATP-binding cassette transporter 1 (ABCA1) R219K (rs2230806) and M883I (rs4149313) polymorphisms and atherosclerosis (AS), but results remain controversial. The purpose of the present study is to investigate whether these two polymorphisms facilitate the susceptibility to AS using a meta-analysis. METHODS PubM...

OBJECTIVE To review possible associations reported between genetic variants and the risk, therapeutic response and prognosis of heart failure. METHODS Electronic databases (PubMed, Web of Science and CNKI) were systematically searched for relevant papers, published between January 1995 and February 2015. RESULTS Eighty-two articles covering 29 genes and 39 polymorphisms were identified. C...

We address leadership emergence and the possibility that there is a partially innate predisposition to occupy a leadership role. Employing twin design methods on data from the National Longitudinal Study of Adolescent Health, we estimate the heritability of leadership role occupancy at 24%. Twin studies do not point to specific genes or neurological processes that might be involved. We therefor...

Genetic association analysis on complex phenotypes under a longitudinal design involving pedigrees encounters the problem of correlation within pedigrees, which could affect statistical assessment of the genetic effects. Approaches have been proposed to integrate kinship correlation into the mixed-effect models to explicitly model the genetic relationship. These have proved to be an efficient w...

The population genetic structure of Native Hawaiians has yet to be comprehensively studied, and the ancestral origins of Polynesians remain in question. In this study, we utilized high-resolution genome-wide SNP data and mitochondrial genomes of 148 and 160 Native Hawaiians, respectively, to characterize their population structure of the nuclear and mitochondrial genomes, ancestral origins, and...

Testing for deviations from Hardy-Weinberg equilibrium is a widely recommended practice for population-based genetic association studies. However, current methods for this test assume a simple random sample and may not be appropriate for sample surveys with complex survey designs. In this paper, the authors present a test for Hardy-Weinberg equilibrium that adjusts for the sample weights and co...

Joint testing for the cumulative effect of multiple single-nucleotide polymorphisms grouped on the basis of prior biological knowledge has become a popular and powerful strategy for the analysis of large-scale genetic association studies. The kernel machine (KM)-testing framework is a useful approach that has been proposed for testing associations between multiple genetic variants and many diff...