Predicting Genetic Values: A Kernel-Based Best Linear Unbiased Prediction With Genomic Data

Genomic data provide a valuable source of information for modeling covariance structures, allowing a more accurate prediction of total genetic values (GVs). We apply the kriging concept, originally developed in the geostatistical context for predictions in the low-dimensional space, to the high-dimensional space spanned by genomic single nucleotide polymorphism (SNP) vectors and study its properties in different gene-action scenarios. Two different kriging methods [“universal kriging” (UK) and “simple kriging” (SK)] are presented. As a novelty, we suggest use of the family of Matérn covariance functions to model the covariance structure of SNP vectors. A genomic best linear unbiased prediction (GBLUP) is applied as a reference method. The three approaches are compared in a whole-genome simulation study considering additive, additive-dominance, and epistatic gene-action models. Predictive performance is measured in terms of correlation between true and predicted GVs and average true GVs of the individuals ranked best by prediction. We show that UK outperforms GBLUP in the presence of dominance and epistatic effects. In a limiting case, it is shown that the genomic covariance structure proposed by VanRaden (2008) can be considered as a covariance function with corresponding quadratic variogram. We also prove theoretically that if a specific linear relationship exists between covariance matrices for two linear mixed models, the GVs resulting from BLUP are linked by a scaling factor. Finally, the relation of kriging to other models is discussed and further options for modeling the covariance structure, which might be more appropriate in the genomic context, are suggested

Comparison of classification methods for detecting associations between SNPs and chick mortality

Multi-category classification methods were used to detect SNP-mortality associations in broilers. The objective was to select a subset of whole genome SNPs associated with chick mortality. This was done by categorizing mortality rates and using a filter-wrapper feature selection procedure in each of the classification methods evaluated. Different numbers of categories (2, 3, 4, 5 and 10) and three classification algorithms (naïve Bayes classifiers, Bayesian networks and neural networks) were compared, using early and late chick mortality rates in low and high hygiene environments. Evaluation of SNPs selected by each classification method was done by predicted residual sum of squares and a significance test-related metric. A naïve Bayes classifier, coupled with discretization into two or three categories generated the SNP subset with greatest predictive ability. Further, an alternative categorization scheme, which used only two extreme portions of the empirical distribution of mortality rates, was considered. This scheme selected SNPs with greater predictive ability than those chosen by the methods described previously. Use of extreme samples seems to enhance the ability of feature selection procedures to select influential SNPs in genetic association studies

Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury

BACKGROUND & AIMS: Drug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine. METHODS: We analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls). RESULTS: Of the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively). CONCLUSIONS: In analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH

An exploratory genome-wide analysis of genetic risk for alcoholic hepatitis

To elucidate the genetic variability between heavy drinkers with and without alcoholic hepatitis

Concentración, segregación y movilidad residencial de los extranjeros en Barcelona

El artículo analiza la dinámica residencial de la población extranjera en la ciudad de Barcelona, considerando tres aspectos que centran su distribución: la concentración en el territorio, la segregación residencial en relación con la población de la ciudad y la movilidad residencial en interrelación con su región metropolitana. Se realiza un análisis temporal que sigue la evolución de estos elementos a lo largo de la década, con el objetivo de aportar una visión de conjunto de los cambios observados. El análisis contempla la utilización de diferentes fuentes estadísticas y detalla el comportamiento de las nacionalidades con más efectivos en Barcelona. Los resultados indican un desplazamiento de las áreas de concentración desde el centro histórico hacia la periferia de la ciudad, un descenso de la segregación vinculado a una mayor dispersión territorial y una fuerte movilidad residencial dentro de la Región Metropolitana que afecta especialmente a los municipios situados en la periferia más próxima a la ciudad.L'article analitza la dinàmica residencial de la població estrangera a la ciutat de Barcelona, considerant tres dels aspectes que en centren la distribució: la concentració en el territori, la segregació residencial en relació amb la població de la ciutat i la mobilitat residencial en interrelació amb la seva regió metropolitana. S'hi realitza una anàlisi temporal que ressegueix l'evolució d'aquests elements al llarg de la darrera dècada, amb l'objectiu d'aportar una visió de conjunt dels canvis observats. L'estudi contempla la utilització de diferents fonts estadístiques i detalla el comportament de les nacionalitats amb més efectius a Barcelona. Els resultats indiquen un desplaçament de les àrees de concentració des del centre històric cap a la perifèria de la ciutat, un descens de la segregació lligat a una dispersió territorial més gran i una forta mobilitat residencial dins de la Regió Metropolitana que afecta especialment els municipis situats a la perifèria més pròxima a la ciutat.L'article analyse la dynamique résidentielle de la population étrangère dans la ville de Barcelone en se concentrant sur trois aspects de sa distribution : la concentration sur le territoire, la ségrégation et la mobilité résidentielle au sein de la région métropolitaine. L'évolution de ces trois facteurs a été suivie pendant une décennie dans le but d'obtenir une vision globale des changements observés. Diverses sources statistiques qui détaillent le comportement des populations les plus nombreuses habitant Barcelone ont été utilisées. Les résultats montrent un déplacement des zones de concentration des étrangers depuis le centre historique vers les périphéries, une diminution de la ségrégation due à la croissante dispersion territoriale, et finalement une forte mobilité résidentielle dans la Région Métropolitaine, particulièrement dans les communes les plus proches de Barcelone.Three aspects of foreigners' residential mobility in the city of Barcelona are studied in this paper: territorial concentration, segregation and residential change within the metropolitan region. To obtain a global view, these three elements are followed for a decade. Several data bases, specifying the behaviour of major nationalities, are used. Results firstly show that foreigners are gradually moving out of the historical centre and into the periphery. Secondly, that there is a strong intra-metropolitan mobility, particularly so in the municipalities nearest to the central city. Finally, as foreigners are more widely distributed throughout the territory, they are also becoming less segregated

A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury

Background & Aims We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. Methods We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings. Results We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28–1.62; P = 1.2 × 10–9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09–1.99; P = .01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32–1.98; P = 4.0 × 10–6; allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21–1.56; P = 1.5 × 10–6; allele frequency = 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. Conclusions In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI

Influence of Genetic Interactions on Polygenic Prediction

Prediction of phenotypes from genotypes is an important objective to fulfill the promises of genomics, precision medicine and agriculture. Although it’s now possible to account for the majority of genetic variation through model fitting, prediction of phenotypes remains a challenge, especially across populations that have diverged in the past. In this study, we designed simulation experiments to specifically investigate the role of genetic interactions in failure of polygenic prediction. We found that non-additive genetic interactions can significantly reduce the accuracy of polygenic prediction. Our study demonstrated the importance of considering genetic interactions in genetic prediction

Characteristics of carbonaceous aerosol in a two-week campaign at Ny-Ålesund

The concentrations of organic carbon (OC) and elemental carbon (EC) in total suspended particle (TSP) were investigated at Ny-Ålesund, Svalbard in a two-week campaign. The levels of OC and EC are 0.86 ± 0.27 µgm(-3) (mean ± standard deviation) and 0.19 ± 0.10 µgm(-3), respectively. Back trajectory analysis of air masses arriving at Ny-Ålesund reveals that long-range transport of polluted air play insignificant role in OC and EC levels, to which the potential influence of the local contamination were ascribed. The average OC/EC ratio is 5.41, suggesting the presence of the secondary organic aerosols. The estimated secondary organic carbon (SOC) in TSP is 0.59 µg/m(3), accounting for 64% of the total organic carbon

Source of and potential bio-indicator for the heavy metal pollution in Ny-Ålesund, Arctic

Three kinds of tundra plant samples including Dicranum angustum (a type of boreal bryophyte), Puccinellia phryganodes (a type of fringy plant), Salix polaris (a type of vascular plant) and surface soil were samples in 200 at Ny-Ålesund of the Arctic. The levels of eight heavymetal elements (Hg, Pb, Cd, Cu, Zn, Ni, Fe and Mn) and three metal-like elements (As, Se, Sr) in the plant and soil samples of the areas within previous coal mining activities are significantly higher than those of other areas. The relative accumulation of these elements in these tundra plant samples is consistent with the one in the soil samples, especially in the areas affected by previous coal mining activities. Thus, the pollution is apparently from local coal mining activity. Dicranum angustum has the highest concentrations among those elements, and it can be a good bio-indicator for heavy metal pollution in Ny-Ålesund. Though Ny-Ålesund is less polluted by heavy metal than nearby Northern European human living areas, but much more than the tundras of the Alaska, Greenland and the Antarctic