Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.     

Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits

We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.     

关于Quarter可层化空间

对第二纲的仿紧Quarter可层化空间进行了研究，证明了这类空间含有σ闭离散的稠密子集. 同时给出了实数集的子集是消去拓扑半群，但是不是Quarter可层化空间.     

Mesoderm induction in early Xenopus embryos by heparin-binding growth factors

In early embryonic development the basic body plan arises because cells in different regions become programmed to follow different developmental pathways. We have proposed that in the early amphibian embryo this process of regional specification arises from the action of three different inducing factors, or morphogens, but we have not until now had any idea of their chemical nature. In this paper we report that pure basic fibroblast growth factor (bFGF), at very low concentrations and with high specificity, closely mimics the effect of the ventrovegetal (VV) signal and that the transmission of the natural VV signal can be blocked by heparin, suggesting that it may be a heparin-binding factor such as bFGF.     

Blood 5-hydroxytryptamine in rats with pulmonary hypertension produced by ingestion ofCrotalaria spectabilis seeds

Zusammenfassung Der pulmonare Blutdruck in Ratten kann durch Abfütterung vonCrotalaria spectabilis erhöht werden, ohne die Konzentration des plasmafreien und an die Thrombozyten gebundenen 5-Hydroxytryptamins zu verändern.