1000 Genomes-based metaanalysis identifies 10 novel loci for kidney function

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-Analysis of kidney function based on the estimated glomerular filtration rate (EGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10-8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, wh

Efeitos de rações com níveis crescentes de cana-de-açúcar em substituição à silagem de milho sobre a população de protozoários ciliados no rúmen de ovinos Effects of diets with increasing levels of sugar cane in substitution of corn silage on rumen population ciliate protozoa in sheep

Oito ovinos machos com fístulas ruminais foram delineados em dois quadrados latinos, em quatro períodos de 35 dias cada e quatro tratamentos, compreendendo níveis crescentes de cana-de-açúcar (CA) em substituição à silagem de milho (SM): A) 100% SM; B) 67% SM e 33% CA; C) 33% SM e 67% CA; e D 100% CA, para avaliação da população de protozoários ciliados no rúmen. As concentrações totais de protozoários ciliados no rúmen e de Entodinium diminuíram e os valores de pH do conteúdo ruminal aumentaram linearmente com o incremento das quantidades de cana-de-açúcar na ração. Não houve diferenças entre tratamentos para o volume ruminal e a taxa de passagem da fase líquida do rúmen.<br>Eight rumen fistulated rams were delineated in two Latin Squares in four periods of 35 days each and four treatments consisted of increasing levels of sugar cane (SC) in substitution to the corn silage (CS): A) 100% CS, B) 67% CS and 33% SC, C) 33% CS and 67% SC and D) 100% SC, to evaluate the population of ciliate protozoa in the rumen. The total concentrations of rumen ciliate protozoa and of Entodinium decreased and the values of pH of the ruminal content increased linearly as dietary sugar cane levels increased. No differences between treatments were observed for the rumen volume and the rumen liquid turnover rate

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBP

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized vari

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of