Imputation-Based Analysis of Association Studies: Candidate Regions and Quantitative Traits

We introduce a new framework for the analysis of association studies, designed to allow untyped variants to be more effectively and directly tested for association with a phenotype. The idea is to combine knowledge on patterns of correlation among SNPs (e.g., from the International HapMap project or resequencing data in a candidate region of interest) with genotype data at tag SNPs collected on a phenotyped study sample, to estimate (“impute”) unmeasured genotypes, and then assess association between the phenotype and these estimated genotypes. Compared with standard single-SNP tests, this approach results in increased power to detect association, even in cases in which the causal variant is typed, with the greatest gain occurring when multiple causal variants are present. It also provides more interpretable explanations for observed associations, including assessing, for each SNP, the strength of the evidence that it (rather than another correlated SNP) is causal. Although we focus on association studies with quantitative phenotype and a relatively restricted region (e.g., a candidate gene), the framework is applicable and computationally practical for whole genome association studies. Methods described here are implemented in a software package, Bim-Bam, available from the Stephens Lab website http://stephenslab.uchicago.edu/software.html

Vulnerability Factors and Pathways Leading to Underage Entry into Sex Work in two Mexican-US Border Cities

The current wave of interest in human trafficking and the commercial sexual exploitation of children has exposed a lack of knowledge about the vulnerabilities leading to underage entry into sex work. This knowledge is necessary for the development of effective prevention programs to identify girls who are most at-risk, especially in Latin America, a region that is believed to be a large source of persons moved across international borders for the purposes of sexual and labor exploitation. The objective of this study was to explore and increase understanding of the vulnerability factors and pathways leading to underage entry into sex work experienced by women currently engaging in sex work in two cities on the northern border of Mexico. From August 2013 to October 2014, 20 female sex workers (FSWs) with a history of entry into sex work prior to age 18 were recruited for in-depth interviews from a larger time-location sample of female sex workers (FSWs) participating in a quantitative survey in Tijuana and Ciudad Juarez. The median age of entry into sex work was 14 (range 10-17); 12/21 participants reported being forced into sex work and, of these, 7 were transported to another city where they began engaging in sex work. Family dysfunction (e.g., domestic violence between parents, parent drug use, neglect, etc.), sexual and physical abuse, and teen pregnancy were among the key themes that emerged as vulnerabilities to underage entry into sex work. Women’s narratives clearly illustrated that the vulnerabilities and pathways leading to underage entry are manifold, complex, and often intersect with each other. Our findings begin to lay the groundwork for understanding the potential vulnerabilities and pathways leading to underage entry into sex, and may have relevance to Latin America in general. This study also provides a foundation for further research to explore what may mitigate these vulnerabilities as well as creating evidence-based interventions to prevent commercial sexual exploitation of minors in the region

Are your covariates under control? How normalization can re-introduce covariate effects

Many statistical tests rely on the assumption that the residuals of a model are normally distributed. Rank-based inverse normal transformation (INT) of the dependent variable is one of the most popular approaches to satisfy the normality assumption. Studies regularly adjust for covariates and then normalize the residuals. This study investigated the effect of regressing covariates against the dependent variable and then applying rank-based INT to the residuals. The correlation between the dependent variable and covariates at each stage of processing was assessed. An alternative approach was tested of applying rank-based INT to the dependent variable before regressing covariates was tested. Analyses based on both simulated and real data examples demonstrated that applying rank-based INT to the dependent variable residuals after regressing out covariates re-introduces a linear correlation between the dependent variable and covariates in almost all situations. This will increase type-1 errors and reduce power. Our proposed alternative approach, where rank-based INT was applied prior to controlling for covariate effects, gave residuals that were normally distributed and linearly uncorrelated with covariates. This approach is therefore recommended

A high density recombination map of the pig reveals a correlation between sex-specific recombination and GC content

<p>Abstract</p> <p>Background</p> <p>The availability of a high-density SNP genotyping chip and a reference genome sequence of the pig (<it>Sus scrofa</it>) enabled the construction of a high-density linkage map. A high-density linkage map is an essential tool for further fine-mapping of quantitative trait loci (QTL) for a variety of traits in the pig and for a better understanding of mechanisms underlying genome evolution.</p> <p>Results</p> <p>Four different pig pedigrees were genotyped using the Illumina PorcineSNP60 BeadChip. Recombination maps for the autosomes were computed for each individual pedigree using a common set of markers. The resulting genetic maps comprised 38,599 SNPs, including 928 SNPs not positioned on a chromosome in the current assembly of the pig genome (build 10.2). The total genetic length varied according to the pedigree, from 1797 to 2149 cM. Female maps were longer than male maps, with a notable exception for SSC1 where male maps are characterized by a higher recombination rate than females in the region between 91–250 Mb. The recombination rates varied among chromosomes and along individual chromosomes, regions with high recombination rates tending to cluster close to the chromosome ends, irrespective of the position of the centromere. Correlations between main sequence features and recombination rates were investigated and significant correlations were obtained for all the studied motifs. Regions characterized by high recombination rates were enriched for specific GC-rich sequence motifs as compared to low recombinant regions. These correlations were higher in females than in males, and females were found to be more recombinant than males at regions where the GC content was greater than 0.4.</p> <p>Conclusions</p> <p>The analysis of the recombination rate along the pig genome highlighted that the regions exhibiting higher levels of recombination tend to cluster around the ends of the chromosomes irrespective of the location of the centromere. Major sex-differences in recombination were observed: females had a higher recombination rate within GC-rich regions and exhibited a stronger correlation between recombination rates and specific sequence features.</p

Local adaptations of Mediterranean sheep and goats through an integrative approach

Small ruminants are suited to a wide variety of habitats and thus represent promising study models for identifying genes underlying adaptations. Here, we considered local Mediterranean breeds of goats (n = 17) and sheep (n = 25) from Italy, France and Spain. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original cradle (i.e., the geographical area in which the breed has emerged), including transhumant pastoral areas. We then used the programs PCAdapt and LFMM to identify signatures of artificial and environmental selection. Considering cradles instead of current GPS coordinates resulted in a greater number of signatures identified by the LFMM analysis. The results, combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles in relation to the gradient of aridity and altitude. Some of these genes have been previously implicated in lipid metabolism (SUCLG2, BMP2), hypoxia stress/lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). Selection signatures involving the PCDH9 and KLH1 genes, as well as NBEA/NBEAL1, were identified in both species and thus could play an important adaptive role

Very high frequency gravitational wave background in the universe

Astrophysical sources of high frequency gravitational radiation are considered in association with a new interest to very sensitive HFGW receivers required for the laboratory GW Hertz experiment. A special attention is paid to the phenomenon of primordial black holes evaporation. They act like black body to all kinds of radiation, including gravitons, and, therefore, emit an equilibrium spectrum of gravitons during its evaporation. Limit on the density of high frequency gravitons in the Universe is obtained, and possibilities of their detection are briefly discussed.Comment: 14 page

Modulation of the gut microbiota of Pacific white shrimp ( Penaeus vannamei Boone, 1931) by dietary inclusion of a functional yeast cell wall‐based additive

Several eco-friendly natural substances can enhance the shrimp immune defence system therby acting as a prophylactic agent in feed additives. Agents such as (1, 3)-(1, 6)-D β-glucan and complex mannan-oligosaccharides located in yeast cell walls present such immunomodulatory and potential prebiotic properties. The aim of our study was to evaluate the effect of a commercial yeast cell wall extract (YCW) on shrimp performance and health status, and influence on gut microbiota. Juvenile Penaeus vannamei (Boone, 1931) were raised at an intensive shrimp farm and fed with two different diet inclusions levels of YCW, that is, 0.5% and 1.0%, in addition to a yeast free control group. After 102 days, animals were sampled, and standard nutrition performance parameters were measured. Additionally, the phylogenetic profile and composition of shrimp gut microbiota were evaluated. Animal performance, including growth and survival, was significantly better on animals fed with YCW than the control group. Furthermore, beneficial bacteria phylotypes were stimulated by the presence of YCW, positively modulating the gut microbiota, with emphasis on 1.0% YCW treatment. Therefore, YCW can be regarded as a prophylactic functional agent in the intensive rearing of juvenile P. vannamei thus improving animal performance and contributing to a healthy intestinal microbiota

Gravitational wave detection using electromagnetic modes in a resonance cavity

We present a proposal for a gravitational wave detector, based on the excitation of an electromagnetic mode in a resonance cavity. The mode is excited due to the interaction between a large amplitude electromagnetic mode and a quasi-monochromatic gravitational wave. The minimum metric perturbation needed for detection is estimated to the order 7.10^(-23) using current data on superconducting niobium cavities. Using this value together with different standard models predicting the occurrence of merging neutron star or black hole binaries, the corresponding detection rate is estimated to 1-20 events per year, with a `table top' cavity of a few meters length.Comment: 8 pages, 1 figure, references adde

Charged multifluids in general relativity

The exact 1+3 covariant dynamical fluid equations for a multi-component plasma, together with Maxwell's equations are presented in such a way as to make them suitable for a gauge-invariant analysis of linear density and velocity perturbations of the Friedmann-Robertson-Walker model. In the case where the matter is described by a two component plasma where thermal effects are neglected, a mode representing high-frequency plasma oscillations is found in addition to the standard growing and decaying gravitational instability picture. Further applications of these equations are also discussed.Comment: 14 pages (example added), to appear in Class. Quantum Gra

Transverse Wave Propagation in Relativistic Two-fluid Plasmas in de Sitter Space

We investigate transverse electromagnetic waves propagating in a plasma in the de Sitter space. Using the 3+1 formalism we derive the relativistic two-fluid equations to take account of the effects due to the horizon and describe the set of simultaneous linear equations for the perturbations. We use a local approximation to investigate the one-dimensional radial propagation of Alfv\'en and high frequency electromagnetic waves and solve the dispersion relation for these waves numerically.Comment: 19 pages, 12 figure