A saturated map of common genetic variants associated with human height.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Evaluation of rods deformation of metal lattice structure in additive manufacturing based on skeleton extraction technology

&lt;abstract&gt; &lt;p&gt;The components with lattice structure as filling unit have great application potential in aerospace and other fields. The failure of the lattice structure directly affects the functional characteristics of the parts filled with the lattice structure. Aiming at the problem that it is difficult to evaluate the deformation degree of metal lattice structure after mechanical loading in additive manufacturing, firstly, the point cloud model of lattice structure is obtained by using CT scanning and three-dimensional reconstruction, and then the skeleton of lattice structure is automatically extracted based on ${L_1}$ median algorithm. Finally, the deformation angle of rods is measured to evaluate the degree of deformation and damage of parts. In this paper, the deformation evaluation of the rods of the BCC lattice is discussed. The experimental results show that the proposed skeleton extraction technology achieves the evaluation of lattice structure deformation. The experimental model is extended to BCC lattice structure with unit cell number of $n \times n \times n$. When the ratio of the rods with more than 40% severe deformation to all rods in the lattice structure reaches $(2n - 1)/2{n^2}$ it indicates that the lattice structure has undergone a large degree of deformation and should not continue to serve.&lt;/p&gt; &lt;/abstract&gt;</jats:p