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.

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Objective: In an effort to inform evidence-based guidelines for clinical practice, we performed a meta-analysis to systematically evaluate the safety and efficacy of Kangai injection (KAI) plus platinum-based chemotherapy for stage III/IV non-small cell lung cancer (NSCLC). Methods: Randomized controlled trials (RCTs) comparing KAI plus platinum-based chemotherapy (experimental group) to chemotherapy alone (control group) were electronically retrieved from the Cochrane Library, PubMed, EMbase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chinese Biological Medicine (CBM) Database, Wanfang Database, and the VIP Database for Chinese Technical Periodicals. RCTs published from the date of inception to July 5, 2018, were included. All trials were assessed for methodological quality in accordance with the Cochrane Reviewer's Handbook for Systematic Reviews of Intervention. Meta-analysis was performed using RevMan5.3 Software and Comprehensive Meta-Analysis (CMA) 2.0. Results: The final analysis included 35 RCTs involving 2,618 patients. Our meta-analysis revealed that KAI combined with platinum-based chemotherapy was associated with significantly greater objective response rate (ORR) (RR=1.36, 95% CI: 1.25-1.49, P<0.00001) and disease control rate (DCR) (RR=1.14, 95% CI: 1.09-1.18, P<0.00001), improvements in quality of life (QOL) (RR=1.75, 95% CI: 1.59-1.93, P<0.00001), and decreases in the incidence of gastrointestinal reactions (RR=0.64, 95% CI: 0.54-0.77, P<0.00001), leukocytopenia (RR=0.54, 95% CI: 0.46-0.63, P<0.00001) and thrombocytopenia (RR=0.52, 95% CI: 0.36-0.76, P=0.0007) when compared with chemotherapy alone. In addition, combined treatment was associated with greater regulation of tumor immune function, as indicated by increases in the proportion of NK, CD3 + , and CD4 + cells (MD=2.27, 95% CI: 1.18-3.36, P<0.0001; MD=12.86, 95% CI: 11.64-14.08, P<0.00001; and MD=5.48, 95% CI: 2.68-8.28, P=0.0001) and decreases in the percentage of CD8 + cells (MD=-2.37, 95% CI from-4.51 to-0.23, P=0.03). Conclusions: From the available evidence, our results indicate that KAI plus platinum-based chemotherapy could be more effective in improving clinical efficacy, decreasing the incidence of adverse reactions and regulating the tumor immune function than chemotherapy alone in the treatment of stage

Background. The objective of this study was to identify potential biomarkers of electroacupuncture (EA) on relieving acute migraine through metabolomic study. Methods. EA treatments were performed on both acupoints and nonacupoints on the nitroglycerin (NTG)-induced migraine rat model. NMR experiments and multivariate analysis were used for metabolomic analysis. Results. The number of head-scratching, the main ethology index of migraine rat model, was significantly increased (P < 0.01) after NTG injection. The plasma metabolic profile of model group was distinct from that of the control group. Glutamate was significantly increased (P < 0.01), whereas lipids were significantly decreased (P < 0.01) in model rats. After EA at acupoints, the metabolic profile of model rats was normalized, with decreased glutamate (P < 0.05) and increased lipids (P < 0.01). In contrast, EA at nonacupoints did not restore the metabolic profile, but with six metabolites significantly different from acupoints group. Interestingly, the number of head-scratching and glutamate level were significantly decreased (P < 0.05) after receiving EA at both acupoints and nonacupoints. Conclusions. EA at acupoints may relieve acute migraine by restoring the plasma metabolic profile and plasma glutamate, while EA at nonacupoints may modestly relieve acute migraine by decreasing plasma glutamate.