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Background: Previous prospective studies highlighted aberrant immunoglobulin G (IgG) N-glycosylation as a risk factor for dementia [such as Alzheimer's disease (AD) and vascular dementia (VaD)]. It is unclear whether this association is causal or explained by confounding or reverse causation.Objective: The aim is to examine the association of genetically predicted IgG N-glycosylation with dementia using 2-sample Mendelian randomization (MR).Methods: Independent genetic variants for IgG N-glycosylation traits were selected as instrument variables from published genome-wide association studies (GWAS) among individuals of European ancestry. We extracted their corresponding summary statistics from large-scale clinically diagnosed AD GWAS dataset and FinnGen biobank VaD GWAS dataset. The inverse variance weighted (IVW) was performed to calculate the effect estimates. Meanwhile, multiple sensitivity analyses were used to assess horizontal pleiotropy and outliers.Results: There were no associations of genetically predicted IgG N-glycosylation traits with the risk of AD and VaD using the IVW method (all Bonferroni corrected p > 0.0013). These estimates of four additional sensitivity analyses methods were consistent with the IVW estimates in terms of direction and magnitude. Additionally, the MR-PRESSO global test and the intercept of MR-Egger regression indicated no evidence of horizontal pleiotropy. Meanwhile, the heterogeneity test showed no significant heterogeneity using the Cochran Q statistic. The leave-one-out sensitivity analyses also did not detect any significant change.Conclusion: Our MR study did not support evidence for the hypothesis that IgG N-glycosylation level may be causally associated with the risk of dementia. [ABSTRACT FROM AUTHOR]

Background: The causal association of C-reactive protein (CRP) and fibrinogen on intracerebral hemorrhage (ICH) remains uncertain. We investigated the causal associations of CRP and fibrinogen with ICH using two-sample Mendelian randomization. Method: We used single-nucleotide polymorphisms associated with CRP and fibrinogen as instrumental variables. The summary data on ICH were obtained from the International Stroke Genetics Consortium (1,545 cases and 1,481 controls). Two-sample Mendelian randomization estimates were performed to assess with inverse-variance weighted and sensitive analyses methods including the weighted median, the penalized weighted median, pleiotropy residual sum and outlier (MR-PRESSO) approaches. MR-Egger regression was used to explore the pleiotropy. Results: The MR analyses indicated that genetically predicted CRP concentration was not associated with ICH, with an odds ratio (OR) of 1.263 (95% CI = 0.935–1.704, p = 0.127). Besides, genetically predicted fibrinogen concentration was not associated with an increased risk of ICH, with an OR of 0.879 (95% CI = 0.060–18.281; p = 0.933). No evidence of pleiotropic bias was detected by MR-Egger. The findings were overall robust in sensitivity analyses. Conclusions: Our findings did not support that CRP and fibrinogen are causally associated with the risk of ICH. [ABSTRACT FROM AUTHOR]

Suboptimal health status (SHS), a physical state between health and disease, is a subclinical and reversible stage of chronic disease. Previous studies have shown alterations in the intestinal microbiota in patients with some chronic diseases. This study aimed to investigate the association between SHS and intestinal microbiota in a case‐control study with 50 SHS individuals and 50 matched healthy controls. Intestinal microbiota was analysed by MiSeq 250PE. Alpha diversity of intestinal microbiota in SHS individuals was higher compared with that of healthy controls (Simpson index, W = 2238, P =.048). Beta diversity was different between SHS and healthy controls (P =.018). At the phylum level, the relative abundance of Verrucomicrobia was higher in the SHS group than that in the controls (W = 2201, P =.049). Compared with that of the control group, nine genera were significantly higher and five genera were lower in abundance in the SHS group (all P <.05). The intestinal microbiota, analysed by a random forest model, was able to distinguish individuals with SHS from the controls, with an area under the curve of 0.79 (95% confidence interval: 0.77‐0.81). We demonstrated that the alteration of intestinal microbiota occurs with SHS, an early stage of disease, which might shed light on the importance of intestinal microbiota in the primary prevention of noncommunicable chronic diseases. [ABSTRACT FROM AUTHOR]

Surface albedo is an important parameter in climate models. The main way to obtain continuous surface albedo for large areas is satellite remote sensing. However, the existing albedo products rarely meet daily-scale requirements, which has a large impact on climate change research and rapid dynamic changes of surface analysis. The Earth Polychromatic Imaging Camera (EPIC) on the Deep Space Climate Observatory (DSCOVR) platform, which was launched into the Sun–Earth's first Lagrange Point (L1) orbit, can provide spectral images of the entire sunlit face of Earth with 10 narrow channels (from 317 to 780 nm). As EPIC can provide high-temporal resolution data, it is beneficial to explore the feasibility of EPIC to estimate high-temporal resolution surface albedo. In this study, hourly surface albedo was calculated based on EPIC observation data. Then, the estimated albedo results were validated by ground-based observations of different land cover types. The results show that the EPIC albedo is basically consistent with the trend of the ground-based observations in the whole time series variation. The diurnal variation of the surface albedo from the hourly EPIC albedo exhibits a "U" shape curve, which has the same trend as the ground-based observations. Therefore, EPIC is helpful to enhance the temporal resolution of surface albedo to diurnal. Surfaces with a three-dimensional structure that casts shadows display the hotspot effect, producing a reflectance peak in the retro-solar direction and lower reflectance at viewing angles away from the solar direction. DSCOVR observes the entire sunlit face of the Earth, which is helpful to make up for the deficiency in the observations of traditional satellites in the hotspot direction in bidirectional reflectance distribution function (BRDF) research, and can help to improve the underestimation of albedo in the direction of hotspot observation. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p > 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54–0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found. [ABSTRACT FROM AUTHOR]