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2022 ◽  
Vol 8 ◽  
Author(s):  
Jiang-Shan Tan ◽  
Meng-Jin Hu ◽  
Yan-Min Yang ◽  
Yue-Jin Yang

Background: Previous observational studies provided conflicting results on the association between low-density lipoprotein cholesterol (LDL-C) level and the risk of Alzheimer's disease (AD).Objective: We used two-sample Mendelian randomization (MR) study to explore the causal associations between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.Methods: Summary-level genetic data for LDL-C were acquired from results of the UK Biobank GWAS. Corresponding data for paternal, maternal, and family history of AD were obtained from the NHGRI-EBI Catalog of human genome-wide association studies. Data for individual AD were obtained from the MR-Base platform. A two-sample MR study was performed to explore the causal association between LDL-C level and the risks of individual, paternal, maternal, and family history of AD.Results: Genetically predicted LDL-C was positively associated with individual [Odds ratio (OR) = 1.509, 95% confidence interval (CI) = 1.140–1.999; P = 4.0 × 10−3], paternal [OR = 1.109, 95% CI = 1.053–1.168; P = 9.5 × 10−5], maternal [OR = 1.132, 95% CI = 1.070–1.199; P = 2.0 × 10−5], and family history of AD [OR = 1.124, 95% CI = 1.070–1.181; P = 3.7 × 10−6] in inverse variance weighted analysis. After performing weighted median and MR-Egger analysis, consistent results were observed. There was no horizontal pleiotropy in the two-sample MR analysis.Conclusions: High level of LDL-C may increase the risks of both individual and familial AD. Decreasing the LDL-C to a reasonable level may help to reduce the related risk.


Author(s):  
Vincent A. Magnotta ◽  
Jia Xu ◽  
Jess G. Fiedorowicz ◽  
Aislinn Williams ◽  
Joseph Shaffer ◽  
...  

2022 ◽  
Vol 17 (1) ◽  
pp. 50-53
Author(s):  
Akira Baba ◽  
Ryo Kurokawa ◽  
Reina Kayama ◽  
Yukiko Tsuneoka ◽  
Mariko Kurokawa ◽  
...  
Keyword(s):  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Wuqing Huang ◽  
Jun Xiao ◽  
Jianguang Ji ◽  
Liangwan Chen

Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors and NPC1L1 inhibitior) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study. Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including eQTLs of drugs target genes, and genetic variants within or nearby drugs target genes associated with LDL cholesterol from GWAS. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates. Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74). No consistent evidence from both analyses was found for other associations. Conclusions: This 2-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization. Funding: Fujian Province Major Science and Technology Program.


2021 ◽  
Vol 12 ◽  
Author(s):  
Min Chen ◽  
Wen-Yan Peng ◽  
Tai-Chun Tang ◽  
Hui Zheng

Background: Previous studies suggested an association of sleep disorders with inflammatory bowel disease (IBD) and indicated that using pharmacological treatments for the modulation of circadian rhythms might prevent IBD pathogenesis or aggravation, but whether the effect of sleep traits on IBD was causal is inconclusive and, therefore, prevents drug repurposing based on the previous studies. We aimed to examine the causal effect of different sleep traits on the pathogenesis of IBD.Methods: Genetic instruments for sleep traits were selected from the largest GWAS studies available in the UK Biobank (n = 449,734) and the 23andMe Research (n = 541,333). A two-sample Mendelian randomization (MR) study was conducted to examine the association of the genetic instruments with IBD (12,882 cases and 21,770 controls), ulcerative colitis (6,968 cases, 20,464 controls), and Crohn’s disease (5,956 cases and 14,927 controls). We applied the inverse-variance weighted (IVW) method to estimate causal effects, and we used the weighted median and MR-Egger method for sensitivity analyses.Results: We found that sleep duration (OR, 1.00, 95% CI 1.00–1.01), short sleep duration (OR, 1.07, 95% CI 0.41–2.83), morningness (OR, 1.05, 95% CI 0.87–1.27), daytime napping (OR, 1.64, 95% CI 0.62–4.4), frequent insomnia (OR, 1.17, 95% CI 0.8–1.72), any insomnia (OR, 1.17, 95% CI 0.69–1.97), and snoring (OR, 0.31, 95% CI 0.06–1.54) had no causal effect on IBD, and these sleep traits had no causal effect on ulcerative colitis and Crohn’s disease either. Most of the sensitivity analyses showed consistent results with those of the IVW method.Conclusion: Our MR study did not support the causal effect of sleep traits on IBD. Pharmacological modulation of circadian rhythms for the prevention of IBD pathogenesis was unwarranted.


Author(s):  
Sebastian Weingärtner ◽  
Kimberly L. Desmond ◽  
Nancy A. Obuchowski ◽  
Bettina Baessler ◽  
Yuxin Zhang ◽  
...  
Keyword(s):  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Masahiro Yoshikawa ◽  
Kensuke Asaba ◽  
Tomohiro Nakayama

Abstract Background As the number of COVID-19 deaths continues to rise worldwide, the identification of risk factors for the disease is an urgent issue, and it remains controversial whether atherogenic lipid-related traits including serum apolipoprotein B, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels, are risk factors. The aim of this study was to estimate causal effects of lipid-related traits on COVID-19 risk in the European population using a two-sample Mendelian randomization (MR) approach. Methods We used summary statistics from a genome-wide association study (GWAS) that included 441,016 participants from the UK Biobank as the exposure dataset of lipid-related traits and from COVID-19 Host Genetics Initiative GWAS meta-analyses of European ancestry as the outcome dataset for COVID-19 susceptibility (32,494 cases and 1,316,207 controls), hospitalization (8316 cases and 1,549,095 controls), and severity (4792 cases and 1,054,664 controls). We performed two-sample MR analyses using the inverse variance weighted (IVW) method. As sensitivity analyses, the MR-Egger regression, weighted median, and weighted mode methods were conducted as were leave-one-out sensitivity analysis, the MR-PRESSO global test, PhenoScanner searches, and IVW multivariable MR analyses. A P value below 0.0055 with Bonferroni correction was considered statistically significant. Results This MR study suggested that serum apolipoprotein B or LDL-cholesterol levels were not significantly associated with COVID-19 risk. On the other hand, we inferred that higher serum triglyceride levels were suggestively associated with higher risks of COVID-19 susceptibility (odds ratio [OR] per standard deviation increase in lifelong triglyceride levels, 1.065; 95% confidence interval [CI], 1.001–1.13; P = 0.045) and hospitalization (OR, 1.174; 95% CI, 1.04–1.33; P = 0.012), and were significantly associated with COVID-19 severity (OR, 1.274; 95% CI, 1.08–1.50; P = 0.004). Sensitivity and bidirectional MR analyses suggested that horizontal pleiotropy and reverse causation were unlikely. Conclusions Our MR study indicates a causal effect of higher serum triglyceride levels on a greater risk of COVID-19 severity in the European population using the latest and largest GWAS datasets to date. However, as the underlying mechanisms remain unclear and our study might be still biased due to possible horizontal pleiotropy, further studies are warranted to validate our findings and investigate underlying mechanisms.


2021 ◽  
Vol 11 (10) ◽  
pp. 964
Author(s):  
Elena Riad Deglow ◽  
Sergio Toledano Gil ◽  
Álvaro Zubizarreta-Macho ◽  
María Bufalá Pérez ◽  
Paulina Rodríguez Torres ◽  
...  

To analyze the effect of a computer-aided static navigation technique and mixed reality technology on the accuracy of orthodontic micro-screw placement. Material and methods: Two hundred and seven orthodontic micro-screws were placed using either a computer-aided static navigation technique (NAV), a mixed reality device (MR), or a conventional freehand technique (FHT). Accuracy across different dental sectors was also analyzed. CBCT and intraoral scans were taken both prior to and following orthodontic micro-screw placement. The deviation angle and horizontal deviation were then analyzed; these measurements were taken at the coronal entry point and apical endpoint between the planned and performed orthodontic micro-screws. In addition, any complications resulting from micro-screw placement, such as spot perforations, were also analyzed across all dental sectors. Results: The statistical analysis showed significant differences between study groups with regard to the coronal entry-point (p < 0.001). The NAV study group showed statistically significant differences from the FHT (p < 0.001) and MR study groups (p < 0.001) at the apical end-point (p < 0.001), and the FHT group found significant differences from the angular deviations of the NAV (p < 0.001) and MR study groups deviations (p = 0.0011). Different dental sectors also differed significantly. (p < 0.001) Additionally, twelve root perforations were observed in the FHT group, while there were no root perforations in the NAV group. Conclusions: Computer-aided static navigation technique enable more accurate orthodontic micro-screw placement and fewer intraoperative complications when compared with the mixed reality technology and conventional freehand techniques.


Author(s):  
Kuang-Mao Chiang ◽  
Wen-Harn Pan

Background: Obesity control and prevention remains challenging. Randomized controlled trials in western countries have demonstrated efficacy of dairy supplementation on fat mass reduction and lean mass increase, when combined with energy restriction protocols. However, there is scanty information on this issue among the East Asian population. Objective: The aim of this study is to investigate the association between milk consumption and weight status in Asian. Design: First, we studied the association between milk intake and body mass index (BMI) changes in a 10-year longitudinal study of Cardiovascular Disease Risk Factor Two-township Study (CVDFACTS) with 1,644 adults. Second, taking advantage of the genetic and phenotype data of 10,000 participants collected by Taiwan Biobank (TWB), we carried out a Mendelian randomization (MR) study to investigate the causal relationship between milk intake and BMI. A lactase persistence genetic marker (rs4954490) was used as the instrumental variable. Results: We found in the longitudinal study that higher baseline milk consumption level was associated with lower odds of increasing BMI or maintaining overweight/obesity status. In the MR study, we found that G allele of the rs4954490, a surrogate of greater milk intake, was associated with lower odds of being obese (BMI > 27 kg/m2); the odds ratio (OR) for the GG versus AA is 0.85 (P = 0.037), and the OR for the GA versus AA is 0.84 (P = 0.032). Conclusions: These findings support current food guide in Asian countries to include dairy group as one of the six food groups for nutrition recommendation.


2021 ◽  
pp. jnumed.121.262232
Author(s):  
Matteo Zanovello ◽  
Gianni Sorarù ◽  
Cristina Campi ◽  
Mariagiulia Anglani ◽  
Alessandro Spimpolo ◽  
...  
Keyword(s):  
Fdg Pet ◽  
18F Fdg ◽  

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