A variational Bayes algorithm for fast and accurate multiple locus genome-wide association analysis

<p>Abstract</p> <p>Background</p> <p>The success achieved by genome-wide association (GWA) studies in the identification of candidate loci for complex diseases has been accompanied by an inability to explain the bulk of heritability. Here, we describe the algorithm V-Bay, a variational Bayes algorithm for multiple locus GWA analysis, which is designed to identify weaker associations that may contribute to this missing heritability.</p> <p>Results</p> <p>V-Bay provides a novel solution to the computational scaling constraints of most multiple locus methods and can complete a simultaneous analysis of a million genetic markers in a few hours, when using a desktop. Using a range of simulated genetic and GWA experimental scenarios, we demonstrate that V-Bay is highly accurate, and reliably identifies associations that are too weak to be discovered by single-marker testing approaches. V-Bay can also outperform a multiple locus analysis method based on the lasso, which has similar scaling properties for large numbers of genetic markers. For demonstration purposes, we also use V-Bay to confirm associations with gene expression in cell lines derived from the Phase II individuals of HapMap.</p> <p>Conclusions</p> <p>V-Bay is a versatile, fast, and accurate multiple locus GWA analysis tool for the practitioner interested in identifying weaker associations without high false positive rates.</p

Mouse obesity network reconstruction with a variational Bayes algorithm to employ aggressive false positive control

<p>Abstract</p> <p>Background</p> <p>We propose a novel variational Bayes network reconstruction algorithm to extract the most relevant disease factors from high-throughput genomic data-sets. Our algorithm is the only scalable method for regularized network recovery that employs Bayesian model averaging and that can internally estimate an appropriate level of sparsity to ensure few false positives enter the model without the need for cross-validation or a model selection criterion. We use our algorithm to characterize the effect of genetic markers and liver gene expression traits on mouse obesity related phenotypes, including weight, cholesterol, glucose, and free fatty acid levels, in an experiment previously used for discovery and validation of network connections: an F2 intercross between the C57BL/6 J and C3H/HeJ mouse strains, where apolipoprotein E is null on the background.</p> <p>Results</p> <p>We identified eleven genes, Gch1, Zfp69, Dlgap1, Gna14, Yy1, Gabarapl1, Folr2, Fdft1, Cnr2, Slc24a3, and Ccl19, and a quantitative trait locus directly connected to weight, glucose, cholesterol, or free fatty acid levels in our network. None of these genes were identified by other network analyses of this mouse intercross data-set, but all have been previously associated with obesity or related pathologies in independent studies. In addition, through both simulations and data analysis we demonstrate that our algorithm achieves superior performance in terms of power and type I error control than other network recovery algorithms that use the lasso and have bounds on type I error control.</p> <p>Conclusions</p> <p>Our final network contains 118 previously associated and novel genes affecting weight, cholesterol, glucose, and free fatty acid levels that are excellent obesity risk candidates.</p

Cultivo de linhaça na entressafra: características fenométricas, fenológicas e produtivas

TCC (graduação)- Universidade Federal de Santa Catarina. Campus Curitibanos. Agronomia.O sul do Brasil apresenta condições edafoclimáticas adequadas para o cultivo e desenvolvimento da cultura da linhaça, entretanto, a falta de materiais técnicos sobre épocas específicas de safra e entressafra resultam em uma desorientação aos produtores. A entressafra pode ser conceituada como o período entre uma safra e outra, período em que o solo geralmente não apresenta cultivo. O experimento foi desenvolvido no campus da UFSC Curitibanos. O objetivo desse trabalho foi caracterizar a fenometria, fenologia e produtividade de plantas de linhaça cultivadas em condições de clima subtropical em diferentes épocas de semeadura durante a entressafra para a microrregião de Curitibanos. O delineamento utilizado foi blocos ao acaso, com quatro blocos e um fator, que foi a época de cultivo. As épocas de cultivo avaliadas foram: E1= 13/08/21; E2= 03/09/21; E3= 17/09/21; E4= 01/10/21; E5= 15/10/21; E6= 05/11/21; E7= 03/12/21; e E8= 15/01/22. Foram marcadas cinco plantas por parcela para as avaliações de crescimento: mensuração de estatura, número total de hastes, altura de inserção de cápsulas e número de folhas verdes na floração. As avaliações de duração do ciclo foram contabilização da duração dos estádios fenológicos e do ciclo total, em dias e em soma térmica. As avaliações de produtividade foram feitas em dez plantas por bloco, sendo elas a contagem de número de cápsula por planta, do número de sementes por cápsula e a massa de mil sementes, além de ter sido estimada a produtividade em t/ha. Os dados meteorológicos foram obtidos do banco de dados, de estações meteorológicas automáticas próximas da área de cultivo. Foram observados maiores valores em estatura e em altura de inserção de cápsulas para os plantios nas duas primeiras épocas, em 13/08 e 03/09, bem como a maior duração do ciclo, com respectivos 125 e 122 dias, e o menor para a época 5, com 86 dias. A época 2 apresentou a maior necessidade térmica, com 1.539,7°C dia para completar o ciclo, e a época 5 a menor necessidade térmica, com 1.272,8°C dia. Para o componente de produtividade número de cápsulas por planta não se observou diferenças entre as épocas. Para o número de sementes por cápsulas o maior valor obtido foi 7,5, sendo similar entre as épocas 1 até a 5. A massa de mil sementes foi maior nas épocas 1 e 2, com 5,85 e 5,87 g respectivamente. As estimativas de produtividade apontaram a época 1 como a mais produtiva, com valores superiores a 2,0 t/ha, não diferindo estatisticamente das épocas 3 e 4. Para os componentes meteorológicos foi possível observar que as épocas 4, 5 e 7 não receberam o mínimo de água necessário para a cultura, e houve a ocorrência de temperaturas superiores a 32°C na fase reprodutiva de todas as épocas, com exceção à época 8.Southern Brazil region has adequate edaphoclimatic potential for the cultivation and development of linseed, however, the lack of technical materials about specific crop seasons and off-seasons cause a disorientation of the producers. The aim of this study was to characterize the growth, phenology and productivity of linseed cultivated under subtropical climate conditions at different growing season during the off-season for the microregion of Curitibanos, SC. The experiments were conducted in the field and organized in randomized blocks, with four blocks and one treatment that was the eight growing season. E1= 13/08/21; E2= 03/09/21; E3= 17/09/21; E4= 01/10/21; E5= 15/10/21; E6= 05/11/21; E7= 03/12/21; e E8= 10/01/22. Five plants for block were marked for the evaluations. The gowth assessments were stature, total number of stems, capsule insertion height and number of green leaves in the flowering. The development evaluations were accounting for the duration of the phenological stages and the total cycle, on thermal sum and days. The productivity assessments were made in ten plants per block, counting the number of capsules per plant, number of seeds per capsule and the mass of thousand seeds, besides that was estimated the yield in t/ha. Meteorological data were obtained from automatic meteorological stations located near experimental area. The greatest values in height and insertion heigh of capsules were observed at seasons E1 and E2. The longest cycle duration was obtained for E1 and E2, with 125 and 122 days, and the shortest duration for E5, with 86 days. The E2 presented the greatest thermal sum, with 1.539,7°C day, while the E5 presented the lowest, with 1.272,8°C day. For the productivity assessment capsules per plant, no diferences were observed between the seasons. For the number of seeds per capsule, the highest value obtained was 7.5, being similar between seasons E1 to E5. The mass of a thousand seeds was higher in seasons E1 and E2, with 5.85 and 5.87 g respectively. The productivity estimated pointed to season E1 as the most productive, with more than 2.0 t/ha, but did not differ statistically from the seasons E3 and E4

X-inactivation informs variance-based testing for X-linked association of a quantitative trait

The X chromosome plays an important role in human diseases and traits. However, few X-linked associations have been reported in genome-wide association studies, partly due to analytical complications and low statistical power. In this study, we propose tests of X-linked association that capitalize on variance heterogeneity caused by various factors, predominantly the process of X-inactivation. In the presence of X-inactivation, the expression of one copy of the chromosome is randomly silenced. Due to the consequent elevated randomness of expressed variants, females that are heterozygotes for a quantitative trait locus might exhibit higher phenotypic variance for that trait. We propose three tests that build on this phenomenon: 1) A test for inflated variance in heterozygous females; 2) A weighted association test; and 3) A combined test. Test 1 captures the novel signal proposed herein by directly testing for higher phenotypic variance of heterozygous than homozygous females. As a test of variance it is generally less powerful than standard tests of association that consider means, which is supported by extensive simulations. Test 2 is similar to a standard association test in considering the phenotypic mean, but differs by accounting for (rather than testing) the variance heterogeneity. As expected in light of X-inactivation, this test is slightly more powerful than a standard association test. Finally, test 3 further improves power by combining the results of the first two tests. We applied the these tests to the ARIC cohort data and identified a novel X-linked association near gene AFF2 with blood pressure, which was not significant based on standard association testing of mean blood pressure. Variance-based tests examine overdispersion, thereby providing a complementary type of signal to a standard association test. Our results point to the potential to improve power of detecting X-linked associations in the presence of variance heterogeneity.https://doi.org/10.1186/s12864-015-1463-

Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis

Objective Weight gain is a side effect of glucocorticoid (GC) use, but the natural history and health implications of changes in weight that occur during the treatment of inflammatory disease are not understood. Methods We evaluated data from the Wegener's Granulomatosis Etanercept Trial. Patients were categorized according to clinical outcome at 1 year: remission (no disease flares), single flare, or multiple flares. Risk factors for gaining ≥10 kg were examined in multivariate models. Results Weights at baseline and 1 year were available for 157 (93%) of the 168 patients analyzed. During year 1, the mean cumulative prednisone dosage in the multiple flares subgroup was 7.9 gm, compared with 6.0 gm and 3.9 gm in the single flare and remission subgroups, respectively ( P 10 kg in the first year of treatment. The quantity of weight gained by patients during treatment has potential future health implications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58632/1/23561_ftp.pd

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

Abstract Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations