Population Structure and Cryptic Relatedness in Genetic Association Studies

We review the problem of confounding in genetic association studies, which arises principally because of population structure and cryptic relatedness. Many treatments of the problem consider only a simple ``island'' model of population structure. We take a broader approach, which views population structure and cryptic relatedness as different aspects of a single confounder: the unobserved pedigree defining the (often distant) relationships among the study subjects. Kinship is therefore a central concept, and we review methods of defining and estimating kinship coefficients, both pedigree-based and marker-based. In this unified framework we review solutions to the problem of population structure, including family-based study designs, genomic control, structured association, regression control, principal components adjustment and linear mixed models. The last solution makes the most explicit use of the kinships among the study subjects, and has an established role in the analysis of animal and plant breeding studies. Recent computational developments mean that analyses of human genetic association data are beginning to benefit from its powerful tests for association, which protect against population structure and cryptic kinship, as well as intermediate levels of confounding by the pedigree.Comment: Published in at http://dx.doi.org/10.1214/09-STS307 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Re-examination of the Relation between Democracy and International Trade The Case of Africa

Scholars and policy makers believe that democracy will bring prosperity through integration into the global economy via increased international trade. This study tests two theories as to why democracies might trade more. First, political freedom may be correlated with economic freedom, thus prompting higher levels of economic activity, thereby driving states to trade more. Second, democracy implies higher quality governance either through institutions or policy-making procedures. I utilize a bilateral gravity trade model covering approximately 150 countries from 1950 to 1999, with fixed effects for time, importers and exporters. I find the theory that democracy, and many of its components, promotes international trade unconvincing. Economic freedom does not have the expected impact on international trade levels, but quality of governance variables have broad economic and statistical significance.trade, democracy, governance, Africa, gravity model

A re-examination of the relation between democracy and international trade: The case of Africa

Scholars and policy makers believe that democracy will bring prosperity through integration into the global economy via increased international trade. This study tests two theories as to why democracies might trade more. First, political freedom may be correlated with economic freedom, thus prompting higher levels of economic activity, thereby driving states to trade more. Second, democracy implies higher quality governance either through institutions or policy-making procedures. I utilize a bilateral gravity trade model covering approximately 150 countries from 1950 to 1999, with fixed effects for time, importers and exporters. I find the theory that democracy, and many of its components, promotes international trade unconvincing. Economic freedom does not have the expected impact on international trade levels, but quality of governance variables have broad economic and statistical significance

Encoding of low-quality DNA profiles as genotype probability matrices for improved profile comparisons, relatedness evaluation and database searches

Many DNA profiles recovered from crime scene samples are of a quality that does not allow them to be searched against, nor entered into, databases. We propose a method for the comparison of profiles arising from two DNA samples, one or both of which can have multiple donors and be affected by low DNA template or degraded DNA. We compute likelihood ratios to evaluate the hypothesis that the two samples have a common DNA donor, and hypotheses specifying the relatedness of two donors. Our method uses a probability distribution for the genotype of the donor of interest in each sample. This distribution can be obtained from a statistical model, or we can exploit the ability of trained human experts to assess genotype probabilities, thus extracting much information that would be discarded by standard interpretation rules. Our method is compatible with established methods in simple settings, but is more widely applicable and can make better use of information than many current methods for the analysis of mixed-source, low-template DNA profiles. It can accommodate uncertainty arising from relatedness instead of or in addition to uncertainty arising from noisy genotyping. We describe a computer program GPMDNA, available under an open source license, to calculate LRs using the method presented in this paper.Comment: 28 pages. Accepted for publication 2-Sep-2016 - Forensic Science International: Genetic

Forensic identification: the Island Problem and its generalisations

In forensics it is a classical problem to determine, when a suspect $S$ shares a property $\Gamma$ with a criminal $C$, the probability that $S=C$. In this paper we give a detailed account of this problem in various degrees of generality. We start with the classical case where the probability of having $\Gamma$, as well as the a priori probability of being the criminal, is the same for all individuals. We then generalize the solution to deal with heterogeneous populations, biased search procedures for the suspect, $\Gamma$-correlations, uncertainty about the subpopulation of the criminal and the suspect, and uncertainty about the $\Gamma$-frequencies. We also consider the effect of the way the search for $S$ is conducted, in particular when this is done by a database search. A returning theme is that we show that conditioning is of importance when one wants to quantify the "weight" of the evidence by a likelihood ratio. Apart from these mathematical issues, we also discuss the practical problems in applying these issues to the legal process. The posterior probabilities of $C=S$ are typically the same for all reasonable choices of the hypotheses, but this is not the whole story. The legal process might force one to dismiss certain hypotheses, for instance when the relevant likelihood ratio depends on prior probabilities. We discuss this and related issues as well. As such, the paper is relevant both from a theoretical and from an applied point of view

Mandatory Vaccination: Why We Still Got to Get Folks to Take Their Shots

Vaccination is widely considered one of the greatest medical achievements of modern civilization. Childhood diseases that were commonplace less than a generation ago are now increasingly rare because of vaccines. In order to be effective at eliminating communicable diseases, vaccines must be administered to sufficient levels of persons in the community. Because of this, public health officials have mandated vaccination for certain diseases as a condition to school attendance. The overwhelming effectiveness of vaccination programs may lead individuals to ignore the benefits of vaccination and focus more on the risk of side effects. Moreover, some have criticized the coercive nature of these programs. These objections may lead to an unacceptably high number of exemptions, which can compromise vaccination programs and leave the population susceptible to outbreaks. This paper explores vaccination programs with an eye toward greater public safety without ignoring the reality of a small but committed group of vaccine critics. The paper begins with a discussion of the historical development of mandatory vaccination policies and the issues posed by exemptions. It then addresses some of these issues in the context of vaccine safety. It also seeks solution by framing the discussion in economic terms. It concludes by recommending stricter enforcement of mandatory requirements for most vaccines and greater dissemination of information on the continued importance of vaccination

Evaluation of low-template DNA profiles using peak heights

In recent years statistical models for the analysis of complex (low-template and/or mixed) DNA profiles have moved from using only presence/absence information about allelic peaks in an electropherogram, to quantitative use of peak heights. This is challenging because peak heights are very variable and affected by a number of factors. We present a new peak-height model with important novel features, including over- and double-stutter, and a new approach to dropin. Our model is incorporated in open-source R code likeLTD. We apply it to 108 laboratory-generated crime-scene profiles and demonstrate techniques of model validation that are novel in the field. We use the results to explore the benefits of modeling peak heights, finding that it is not always advantageous, and to assess the merits of pre-extraction replication. We also introduce an approximation that can reduce computational complexity when there are multiple low-level contributors who are not of interest to the investigation, and we present a simple approximate adjustment for linkage between loci, making it possible to accommodate linkage when evaluating complex DNA profiles

Sovereign Risk, Elections, and Contagion

This paper aims to quantify the political risk effect and its different economic implications in normal and crisis situations through the proxy analysis of election and the sovereign bond spreads. Our study leads to three main findings. First, in normal economic situations, elections and government turnovers expand bond spreads, demonstrating investors' concern over the possibility of government policies or instability brought by the election. During a crisis, however, investors prefer change, indicating hope in new policies ameliorate public finances. Second, due to the prolonged eurozone sovereign debt crisis, elections in European countries have stronger contagion effects in their own region during a global slowdown period than a normal period. However, their effect does not carry over globally after the 2008 financial crisis. Third, results show that the election induced peak shrinks from 3 months before and after the election date to 1–2 months when the economic situation turns from normal to a downgraded period