Search

BackgroundPrevious genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.MethodsWe conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.ResultsThe discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.ConclusionsThis study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Background: Observational studies suggested a bidirectional relationship between severe autoimmune type 2 diabetes and focal epilepsy. However, it remains debated whether and in which direction a causal association exists. This genetics-based study aimed to explore the relationships of severe autoimmune type 2 diabetes (T2DM) and focal epilepsy outcomes with two sample Mendelian randomization (TSMR) method. Methods: Genetic instruments were obtained from large-scale genome-wide meta-analysis of severe autoimmune T2DM (Ncase = 452, Ncontrol = 2,744), and focal epilepsy (Ncase = 929, Ncontrol = 212,532) of European ancestry. A series of analyses were performed to select eligible genetic instruments robustly associated with each of the traits using summary-level statistics. Inverse variance weighted was used for primary analysis, with alternative 11 MR methods. A scatter plot was utilized to illustrate the association between single nucleotide polymorphism (SNP) effects on the exposure and SNP effects on the outcome. The Wald ratio for individual SNPs and their cumulative effects was depicted using a forest plot. And diagnostics and sensitivity analyses were used to evaluate if the causal estimates are robust to violations of MR underlying assumptions, including pleiotropy, heterogeneity assessment, and leave-one-out analysis. Then the results were validated using CURATED database of DisGeNET platform. Results: For forward analysis, genetic predisposition to severe autoimmune T2DM was associated with an increased risk of focal epilepsy (Inverse variance weighted (IVW) method: OR = 1.11, 95% CI = 1.03-1.18, p = 0.012). For reverse analysis, there was no enough instrument variables of focal epilepsy on severe autoimmune T2DM. Further, the interrelation between severe autoimmune T2DM and focal epilepsy was demonstrated via variant-disease association network analysis using the instrument SNPs. Discussion: This MR study supports a causal link between severe autoimmune T2DM and focal epilepsy. More effort should be made to screen seizure in severe autoimmune T2DM, unravel its clinical implications, and explore its role as a putative modifiable risk factor. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Tourism Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In order to solve the problems of low measurement efficiency and high safety risks of personnel working on the line faced by the traditional single-point measurement means in the cross-section measurement of existing lines, vehicle-mounted mobile measurement technology was adopted to carry out the application research of cross-section measurement of existing railroads, and the process and method of technology application were introduced from three aspects: acquisition equipment, data acquisition and data solving. Based on the LiDAR point cloud of the whole section along the railroad line rapidly collected by the technology, the rail model reconstruction and route center extraction method with POS trajectory line guidance and two-step ICP alignment was proposed, and on this basis, the data processing method of section point cloud segmentation and attribute point automatic calculation was designed, which realized the rapid batch production of the results of the cross-sectional measurement of the existing railway lines. Combined with the application of a railroad project to build a second line, the results show that: the elevation accuracy is 19. 2 mm, distance accuracy is 16. 1 mm, which meet the specification requirements of the reconstruction of railroad engineering measurement. The method can effectively improve the efficiency of the existing line cross-section measurement, significantly reduce the amount of on-line work, and change the status that railroad crosssection measurement mainly depends on the manpower, which provides technical support and safety guarantee for the existing railroad cross-section fast measurement. [ABSTRACT FROM AUTHOR]

The study explored the feasibility of producing protein feed by microbial enzyme synergy fermentation of feather meal and to determine the process parameters for this production. The keratin-degrading bacterial strains selected from the laboratory were combined with commercially available keratinase enzyme preparations to utilize microbial enzyme synergy in solid-state fermentation of feather meal. The in vitro pepsin digestibility was used as the index to analyze the fermentation time, inoculation amount, microbial enzyme ratio, and water addition through single-factor and orthogonal test analysis. The results showed that the optimal fermentation process was obtained: The water addition to feather meal was 45%, the microbial enzyme ratio was 1:1, the inoculation amount was 6%, and the fermentation time was 7 days. After fermentation, the in vitro pepsin digestibility of feather meal was 63.97%, which was significantly improved by 15.22% compared to before fermentation (P<0.01), and the soluble protein content was 3.51 g/L, which was significantly increased by 80% compared to before fermentation (P<0.05). The study indicates that under the optimal process parameters, using microbial enzyme synergy in solid-state fermentation of feather meal can efficiently produce protein feed and enhance the feed value of feather meal. [ABSTRACT FROM AUTHOR]