Estimation of Jacquard's genetic identity coefficients with bi-allelic variants by constrained least-squares.

The Jacquard genetic identity coefficients are of fundamental importance in relatedness research. We address the estimation of these coefficients as well as other relationship parameters that derive from them such as kinship and inbreeding coefficients using a concise matrix framework. Estimation of the Jacquard coefficients via likelihood methods and the expectation-maximization algorithm is computationally very demanding for large numbers of polymorphisms.

Improved approximation and visualization of the correlation matrix.

The graphical representation of the correlation matrix by means of different multivariate statistical methods is reviewed, a comparison of the different procedures is presented with the use of an example data set, and an improved representation with better fit is proposed. Principal component analysis is widely used for making pictures of correlation structure, though as shown a weighted alternating least squares approach that avoids the fitting of the diagonal of the correlation matrix outperforms both principal component analysis and principal factor analysis in approximating a correlation matrix. Weighted alternating least squares is a very strong competitor for principal component analysis, in particular if the correlation matrix is the focus of the study, because it improves the representation of the correlation matrix, often at the expense of only a minor percentage of explained variance for the original data matrix, if the latter is mapped onto the correlation biplot by regression.

The transitivity of the Hardy-Weinberg law.

The Hardy-Weinberg law is shown to be transitive in the sense that a multi-allelic polymorphism that is in equilibrium will retain its equilibrium status if any allele together with its corresponding genotypes is deleted from the population. Similarly, the transitivity principle also applies if alleles are joined, which leads to the summation of allele frequencies and their corresponding genotype frequencies. These basic polymorphism properties are intuitive, but they have apparently not been formalized or investigated.

Using compositional mixed-effects models to evaluate responses to amino acid supplementation in milk replacers for calves.

The consequences of supplementing Lys, Met, and Thr in milk replacers (MR) for calves have been widely studied, but scarce information exists about potential roles of other AA (whether essential or not). The effects on growth performance of supplementation of 4 different AA combinations in a mixed ration (25.4% crude protein and 20.

A network algorithm for the X chromosomal exact test for Hardy-Weinberg equilibrium with multiple alleles.

Statistical methodology for testing the Hardy-Weinberg equilibrium at X chromosomal variants has recently experienced considerable development. Up to a few years ago, testing X chromosomal variants for equilibrium was basically done by applying autosomal test procedures to females only. At present, male alleles can be taken into account in asymptotic and exact test procedures for both the bi- and multiallelic case.

Some thoughts on counts in sequencing studies.

Measurements in sequencing studies are mostly based on counts. There is a lack of theoretical developments for the analysis and modelling of this type of data. Some thoughts in this direction are presented, which might serve as a seed.

A likelihood ratio approach for identifying three-quarter siblings in genetic databases.

The detection of family relationships in genetic databases is of interest in various scientific disciplines such as genetic epidemiology, population and conservation genetics, forensic science, and genealogical research. Nowadays, screening genetic databases for related individuals forms an important aspect of standard quality control procedures. Relatedness research is usually based on an allele sharing analysis of identity by state (IBS) or identity by descent (IBD) alleles.

Goodness-of-fit filtering in classical metric multidimensional scaling with large datasets.

Metric multidimensional scaling (MDS) is a widely used multivariate method with applications in almost all scientific disciplines. Eigenvalues obtained in the analysis are usually reported in order to calculate the overall goodness-of-fit of the distance matrix. In this paper, we refine MDS goodness-of-fit calculations, proposing additional point and pairwise goodness-of-fit statistics that can be used to filter poorly represented observations in MDS maps.

Assessment of kinship detection using RNA-seq data.

Analysis of RNA sequencing (RNA-seq) data from related individuals is widely used in clinical and molecular genetics studies. Prediction of kinship from RNA-seq data would be useful for confirming the expected relationships in family based studies and for highlighting samples from related individuals in case-control or population based studies. Currently, reconstruction of pedigrees is largely based on SNPs or microsatellites, obtained from genotyping arrays, whole genome sequencing and whole exome sequencing.

Bayesian model selection for the study of Hardy-Weinberg proportions and homogeneity of gender allele frequencies.

Standard statistical tests for Hardy-Weinberg equilibrium assume the equality of allele frequencies in the sexes, whereas tests for the equality of allele frequencies in the sexes assume Hardy-Weinberg equilibrium. This produces a circularity in the testing of genetic variants, which has recently been resolved with new frequentist likelihood and exact procedures. In this paper, we tackle the same problem by posing it as a Bayesian model comparison problem.

A Log-Ratio Biplot Approach for Exploring Genetic Relatedness Based on Identity by State.

The detection of cryptic relatedness in large population-based cohorts is of great importance in genome research. The usual approach for detecting closely related individuals is to plot allele sharing statistics, based on identity-by-state or identity-by-descent, in a two-dimensional scatterplot. This approach ignores that allele sharing data across individuals has in reality a higher dimensionality, and neither regards the compositional nature of the underlying counts of shared genotypes.

Exploration of geochemical data with compositional canonical biplots.

The study of the relationships between two compositions is of paramount importance in geochemical data analysis. This paper develops a compositional version of canonical correlation analysis, called CoDA-CCO, for this purpose. We consider two approaches, using the centred log-ratio transformation and the calculation of all possible pairwise log-ratios within sets.

Multi-allelic exact tests for Hardy-Weinberg equilibrium that account for gender.

Statistical tests for Hardy-Weinberg equilibrium are important elementary tools in genetic data analysis. X-chromosomal variants have long been tested by applying autosomal test procedures to females only, and gender is usually not considered when testing autosomal variants for equilibrium. Recently, we proposed specific X-chromosomal exact test procedures for bi-allelic variants that include the hemizygous males, as well as autosomal tests that consider gender.

On the testing of Hardy-Weinberg proportions and equality of allele frequencies in males and females at biallelic genetic markers.

Standard statistical tests for equality of allele frequencies in males and females and tests for Hardy-Weinberg equilibrium are tightly linked by their assumptions. Tests for equality of allele frequencies assume Hardy-Weinberg equilibrium, whereas the usual chi-square or exact test for Hardy-Weinberg equilibrium assume equality of allele frequencies in the sexes. In this paper, we propose ways to break this interdependence in assumptions of the two tests by proposing an omnibus exact test that can test both hypotheses jointly, as well as a likelihood ratio approach that permits these phenomena to be tested both jointly and separately.

A Bayesian test for Hardy-Weinberg equilibrium of biallelic X-chromosomal markers.

The X chromosome is a relatively large chromosome, harboring a lot of genetic information. Much of the statistical analysis of X-chromosomal information is complicated by the fact that males only have one copy. Recently, frequentist statistical tests for Hardy-Weinberg equilibrium have been proposed specifically for dealing with markers on the X chromosome.

Graphics for relatedness research.

Studies of relatedness have been crucial in molecular ecology over the last decades. Good evidence of this is the fact that studies of population structure, evolution of social behaviours, genetic diversity and quantitative genetics all involve relatedness research. The main aim of this article was to review the most common graphical methods used in allele sharing studies for detecting and identifying family relationships.

A genome-wide study of Hardy-Weinberg equilibrium with next generation sequence data.

Statistical tests for Hardy-Weinberg equilibrium have been an important tool for detecting genotyping errors in the past, and remain important in the quality control of next generation sequence data. In this paper, we analyze complete chromosomes of the 1000 genomes project by using exact test procedures for autosomal and X-chromosomal variants. We find that the rate of disequilibrium largely exceeds what might be expected by chance alone for all chromosomes.

Testing for Hardy-Weinberg equilibrium at biallelic genetic markers on the X chromosome.

Testing genetic markers for Hardy-Weinberg equilibrium (HWE) is an important tool for detecting genotyping errors in large-scale genotyping studies. For markers at the X chromosome, typically the χ(2) or exact test is applied to the females only, and the hemizygous males are considered to be uninformative. In this paper we show that the males are relevant, because a difference in allele frequency between males and females may indicate HWE not to hold.

Correlation between tobacco control policies, consumption of rolled tobacco and e-cigarettes, and intention to quit conventional tobacco, in Europe.

Objective: To analyse the correlation between the implementation of tobacco control policies and tobacco consumption, particularly rolling tobacco, electronic cigarettes (e-cigarettes) users and the intent to quit smoking in 27 countries of the European Union.

Design: Ecological study with the country as the unit of analysis.

Data Sources: We used the data from tobacco control activities, measured by the Tobacco Control Scale (TCS), in 27 European countries, in 2010, and the prevalence of tobacco consumption data from the Eurobarometer of 2012.

Exact Inference for Hardy-Weinberg Proportions with Missing Genotypes: Single and Multiple Imputation.

This paper addresses the issue of exact-test based statistical inference for Hardy-Weinberg equilibrium in the presence of missing genotype data. Missing genotypes often are discarded when markers are tested for Hardy-Weinberg equilibrium, which can lead to bias in the statistical inference about equilibrium. Single and multiple imputation can improve inference on equilibrium.

Statistical inference for Hardy-Weinberg proportions in the presence of missing genotype information.

In genetic association studies, tests for Hardy-Weinberg proportions are often employed as a quality control checking procedure. Missing genotypes are typically discarded prior to testing. In this paper we show that inference for Hardy-Weinberg proportions can be biased when missing values are discarded.

The mid p-value in exact tests for Hardy-Weinberg equilibrium.

Objective: Exact tests for Hardy-Weinberg equilibrium are widely used in genetic association studies. We evaluate the mid p-value, unknown in the genetics literature, as an alternative for the standard p-value in the exact test.

Method: The type 1 error rate and the power of the exact test are calculated for different sample sizes, significance levels, minor allele counts and degrees of deviation from equilibrium.

Similarity in recombination rate estimates highly correlates with genetic differentiation in humans.

Recombination varies greatly among species, as illustrated by the poor conservation of the recombination landscape between humans and chimpanzees. Thus, shorter evolutionary time frames are needed to understand the evolution of recombination. Here, we analyze its recent evolution in humans.