Unraveling the Link: Mendelian Randomization Reveals Causal Relationship Between Selenium and Metabolic Syndrome.

Observational studies have linked selenium and metabolic syndrome (MetS), but the causality remains unclear. Therefore, this study intends to determine the causal relationship between selenium and the risk of MetS and its component features [body mass index (BMI), waist circumference adjusted for BMI (WCadjBMI), triglycerides (TC), HDL-cholesterol (HDL-C), fasting blood glucose (FBG), fasting blood insulin (FBI), systolic blood pressure (SBP), and diastolic blood pressure (DBP)]. This study was designed as the two-sample Mendelian randomization (MR), and genetic variants were obtained from the genome-wide association studies. The inverse variance weighted (IVW) was applied as the primary method, and the MR-Egger, weighted median, and MR-PRESSO were supplemented to assess its robustness. The Bonferroni method was used to correct p-values for multiple tests. Genetically incremented selenium level was related to higher odds ratios of developing the MetS (OR = 1.054, 95% CI = 1.016-1.094, p = 0.0049). As for components, significant causal links were identified between selenium and BMI (ß = 0.015, p = 1.321 × 10-5), WCadjBMI (ß = 0.033, p = 2.352 × 10-4), HDL-C (ß = -0.036, p = 1.352 × 10-8), FBG (ß = 0.028, p = 0.001), and FBI (ß = 0.028, p = 0.002). No significant association was discovered for SBP (ß = -0.076, p = 0.218) and DBP (ß = 0.054, p = 0.227). These results were generally supported by the weighted median and MR-PRESSO methods. Our study provided evidence of the causal effect of selenium on MetS risk from the genetic perspective in the European population, and further investigation across diverse populations was warranted.

Associations of healthy eating index-2015 with osteoporosis and low bone mass density in postmenopausal women: a population-based study from NHANES 2007-2018.

Purpose: The current study aimed to explore the associations of diet quality assessed by healthy eating index-2015 (HEI-2015) with risks of osteoporosis and low bone mineral density (BMD) among American postmenopausal women aged 50 years and older. Methods: Postmenopausal women aged 50 years and older in the National Health and Nutrition Examination Survey from 2007 through 2018 were included in the final sample. Analysis of variance and Rao-Scott adjusted chi-square tests were used to compare the characteristics across tertiles of HEI-2015. Univariate and multivariate weighted logistic regression models were employed to explore the associations of HEI-2015 tertiles and continuous HEI-2015 with the risks of osteoporosis and low BMD. Nonlinear dose-response associations were evaluated using weighted restricted cubic spline analyses, and the contributions of various HEI-2015 components were assessed using weighted quantile sum regression models. Results: The final sample included 3,421 postmenopausal women aged 50 years and older representative for approximately 28.38 million non-institutionalized U.S. postmenopausal women. Osteoporosis prevalence decreased with HEI-2015 tertiles while the prevalence of low BMD showed no significant decrease. Compared with postmenopausal women in the first tertile of HEI-2015, those with the second (OR: 0.57, 95%CI: 0.38-0.84) and third (OR: 0.48, 95%CI: 0.29-0.78) HEI-2015 tertiles were associated with reduced osteoporosis risk after multivariate adjustments, but no significant association of HEI-2015 with the risk of BMD was identified. Furthermore, similar effects were confirmed in the sensitivity analyses and subgroup analyses and interaction effects. Moreover, significant nonlinear associations were observed between HEI-2015 with osteoporosis risk, and total vegetables, refined grains and greens and beans demonstrated the strongest protective effect among HEI-2015 components against osteoporosis. Conclusions: This study strongly suggests the significant negative associations of HEI-2015 with osteoporosis risk in American postmenopausal women. These findings highlight the importance of adherence to the dietary guidelines for Americans in reducing the risk of osteoporosis.

Maternal history of Alzheimer's disease predisposes to altered serum cholesterol levels in adult offspring.

Controversial findings regarding the association between serum cholesterol levels and Alzheimer's disease (AD) have been identified through observational studies. The genetic basis shared by both factors and the causality between them remain largely unknown. The objective of this study is to examine the causal impact of maternal history of AD on changes in serum cholesterol levels in adult offspring. By retrieving genetic variants from summary statistics of large-scale genome-wide association study of maternal history of AD (European-based: Ncase = 27 696, Ncontrol = 260 980). The causal association between genetically predicted maternal history of AD and changes in serum cholesterol levels in adult offspring was examined using the two-sample Mendelian randomization (MR) method. Causal impact estimates were calculated using single-nucleotide polymorphisms in both univariable MR (UMR) and multivariable MR (MVMR) analyses. Additionally, other approaches, such as Cochran's Q test and leave-one-out variant analysis, were employed to correct for potential biases. The results of UMR presented that genetically predicted maternal history of AD was positively associated with hypercholesterolemia (OR = 1.014; 95% CI: 1.009-1.018; p < 0.001), total cholesterol (OR = 1.29; 95% CI: 1.134-1.466; p < 0.001) and low-density lipoprotein (OR = 1.525; 95% CI: 1.272-1.828; p < 0.001) among adult offspring. Genetic predisposition for maternal history of AD to be negatively associated with high-density lipoprotein (OR = 0.889; 95% CI: 0.861-0.917; p < 0.001). The MVMR analysis remained robust and significant after adjusting for diabetes and obesity in offspring. Sufficient evidence was provided in this study to support the putative causal impact of maternal history of AD on the change of serum cholesterol profile in adult offspring. In clinical practice, priority should be given to the detection and monitoring of cholesterol levels in individuals with a maternal history of AD, particularly in the early stages.

Association between dietary flavonoid intake and depressive symptoms: A cross-sectional research.

OBJECTIVE: To investigate the relationship between dietary flavonoid intake and depression symptoms in American adults. METHODS: Data sets were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018 survey cycles. Both males and females aged 18 years and older with complete information about dietary flavonoid intake (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols), depression symptoms, and covariates were included. Logistic regression models were conducted to calculate the odds ratio (OR) of single dietary flavonoid subclass intake on depression, and the restricted cubic spline (RCS) models were utilized to explore the corresponding dose-response relationships. Additionally, we implemented the weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) models to estimate the mixed effects of six flavonoid subclasses and identify the predominant types. RESULTS: After multivariable adjustments, people with higher consumption of flavanones (OR: 0.68, 95% CI: 0.52-0.90, p = 0.008), flavones (OR: 0.63, 95% CI: 0.46-0.87, p = 0.007), flavonols (OR: 0.66, 95% CI: 0.49-0.89, p = 0.008), and total flavonoids (OR: 0.69, 95% CI: 0.50-0.95, p = 0.024) had lower odds of depression symptoms. Meanwhile, significant dose-response relationships were supported by the RCS models. However, no obvious associations between isoflavones, anthocyanidins, flavan-3-ols, and the odds of suffering from depression symptoms were found by the logistic regression models and RCS models. As for the mixed effect, the WQS and qgcomp models both demonstrated that the mixture of six flavonoid subclasses was inversely related to the odds ratios of depression symptoms, and flavones, flavanones, and anthocyanidins were the top 3 contributors. CONCLUSION: Our study implied dietary flavonoid intake was associated with the decreased probability of depression symptoms in U.S. adults, among which flavones, flavanones, and anthocyanidins may occupy the predominant roles.

Chemical Synthesis Creates Single Glycoforms of the Ectodomain of Herpes Simplex Virus-1 Glycoprotein D.

Herpes simplex virus-1 (HSV-1) utilizes multiple viral surface glycoproteins to trigger virus entry and fusion. Among these glycoproteins, glycoprotein D (gD) functions as a receptor-binding protein, which makes it an attractive target for the development of vaccines against HSV-1 infection. Several recombinant gD subunit vaccines have been investigated in both preclinical and clinical phases with varying degrees of success. It is fundamentally critical to explore the functions of gD glycans. In light of this, we report an efficient synthetic platform to construct glycosylated gDs bearing homogeneous glycans at N94 and N121. The oligosaccharides were prepared by enzymatic synthesis and conjugated to peptidyl sectors. The glycoproteins were constructed via a combination of 7-(piperazin-1-yl)-2-(methyl)quinolinyl (PPZQ)-assisted expressed protein ligation and ß-mercapto amino acid-assisted-desulfurization strategies. Biological studies showed that synthetic gDs exhibited potent in vivo activity in mice.

Relationship between dietary carotenoid intake and sleep duration in American adults: a population-based study.

OBJECTIVE: To investigate the relationship between dietary carotenoid intake and sleep duration. METHODS: Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007-2018 without missing information on dietary carotenoid intake (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants' carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short (< 7 h/night), optimal (7-8 h/night), and long (> 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration. RESULTS: Multinominal logistic regression presented that people with higher intakes of α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where ß-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while ß-carotene, α-carotene, and ß-cryptoxanthin were the main factors related to the lower risk of long sleep duration. CONCLUSION: Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers.

Associations of oxidative balance score with total abdominal fat mass and visceral adipose tissue mass percentages among young and middle-aged adults: findings from NHANES 2011-2018.

Objective: This study aimed to explore the association of the oxidative balance score (OBS) with total abdominal fat mass (TAFM) and visceral adipose tissue mass (VATM) percentages among young and middle-aged U.S. adults. Methods: Young and middle-aged adults in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 were included. Analysis of variance and Rao-Scott adjusted chi-square tests were used to compare the characteristics across quartiles of OBS. Univariate and multivariate weighted logistic regression models were employed to explore the relationship between OBS and the risks of high TAFM or high VATM percentage in the general population and subgroups, while the interaction effects were tested with a likelihood test. Weighted restricted cubic spline analyses were utilized to assess the non-linear association of OBS with TAFM and VATM percentages. Results: The final sample included 8,734 young and middle-aged non-institutionalized U.S. adults representing 134.7 million adults. Compared with adults in the first quartile of OBS, those with higher OBS were less likely to have a high TAFM percentage; the ORs and 95% CI for adults in the second, third, and highest quartiles of OBS were 0.70 (0.53-0.94), 0.49 (0.36-0.60), and 0.25 (0.18-0.36), respectively. Similar trends were observed in the association between OBS and VATM percentages. Moreover, similar effects were confirmed in the sensitivity analyses and subgroup analyses according to demographic characteristics. Regarding the OBS subclass, higher dietary OBS and lifestyle OBS were also correlated with decreased ORs of high TAFM and VATM percentages. Conclusion: This study strongly suggests that higher OBS, as well as higher dietary OBS and lifestyle OBS, are significantly correlated with lower risks of abdominal obesity and visceral fat accumulation. The findings highlight the importance of an antioxidant-rich diet and maintaining a healthy lifestyle in reducing the risks.

Genetic association between coffee/caffeine consumption and the risk of obstructive sleep apnea in the European population: a two-sample Mendelian randomization study.

BACKGROUND: The association between coffee/caffeine consumption and obstructive sleep apnea (OSA) risk remains unclear. PURPOSE: To determine the relationship between coffee/caffeine consumption and the risk of OSA, using the Mendelian randomization (MR) method in the European population. METHODS: Two sets of coffee consumption-associated genetic variants were, respectively, extracted from the recent genome-wide meta-analysis (GWMA) and genome-wide association study (GWAS) of coffee consumption. Taking other caffeine sources into account, genetic variants associated with caffeine consumption from tea and plasma caffeine (reflecting total caffeine intake) were also obtained. The inverse variance weighted (IVW) technique was utilized as the primary analysis, supplemented by the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Leave-one-out (LOO) analysis was performed to assess whether the overall casual estimates were driven by a single SNP. Additional sensitivity analyses were performed using similar methods, while the genetic variants associated with confounders, e.g., body mass index and hypertension, were excluded. RESULTS: The IVW method demonstrated that coffee consumption GWMA (OR: 1.065, 95% CI 0.927-1.224, p = 0.376), coffee consumption GWAS (OR: 1.665, 95% CI 0.932-2.977, p = 0.086), caffeine from tea (OR: 1.198, 95% CI 0.936-1.534, p = 0.151), and blood caffeine levels (OR: 1.054, 95% CI 0.902-1.231, p = 0.508) were unlikely to be associated with the risk of OSA. The other three methods presented similar results, where no significant associations were found. No single genetic variant was driving the overall estimates by the LOO analysis. These findings were also supported by the sensitivity analyses with no confounding genetic variants. CONCLUSION: Our study found no association between coffee/caffeine consumption and the risk of OSA.

Association between frailty and depression: A bidirectional Mendelian randomization study.

Frailty and depression were linked in observational studies, but the causality remains ambiguous. We intended to explore it using Mendelian randomization (MR). We obtained frailty genome-wide association study (GWAS) data from UK Biobank and TwinGen meta-analysis, and depression GWAS data from Psychiatric Genomics Consortium (PGC) and FinnGen (respectively recorded as PD and FD). We performed univariable and multivariable-adjusted MR with adjustments for body mass index (BMI) and physical activity (PA). Frailty was significantly associated with elevated risks of PD (OR, 1.860; 95% CI, 1.439 to 2.405; P < 0.001) and FD (OR, 1.745; 95% CI, 1.193 to 2.552; P = 0.004), and depression was meanwhile a susceptible factor for frailty (PD: ß, 0.146; 95% CI, 0.086 to 0.201; P < 0.001; and FD: ß, 0.112; 95% CI, 0.051 to 0.174; P < 0.001). This association was robust after adjustments for BMI or PA. Our study provides evidence of the bidirectional causal association between frailty and depression from genetic perspectives.

Dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2017-2018.

BACKGROUND: Whether there is an association between dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in American adults remains unclear. METHODS: Data came from the National Health and Nutrition Examination Survey 2017-2018. Choline intake was defined by the mean amounts of two 24 h dietary recalls, and choline intake was categorized into three groups according to the quartiles: inadequate (P75). Hepatic steatosis was assessed with FibroScan®, in which VCTE was employed with controlled attenuation to derive the controlled attenuation parameter (CAP), and NAFLD was defined as a CAP score ≥285 dB/m. Multivariable linear regression was performed to assess the linear relationship between choline intake and CAP. Multivariable logistics regression models were conducted to assess the association between choline intake status and NAFLD in the final sample and subgroup analysis was then performed in men and women. RESULTS: The amount of dietary choline was inversely associated with CAP score (ß = -0.262, 95% CI: -0.280, -0.245). Compared to inadequate choline intake, optimal choline intake was related to a lower risk of NAFLD (OR: 0.705, 95% CI: 0.704-0.706) in the final sample. Subgroup analysis by gender revealed that the highest choline intake status was associated with a lower risk of NAFLD both in females (OR: 0.764, 95% CI: 0.762-0.766), and males (OR: 0.955, 95% CI: 0.953-0.958) when compared to the lowest choline intake. CONCLUSIONS: With the latest NHANES data, we found that higher dietary choline was associated with a lower risk of NAFLD in American adults, and such a relationship exists in both females and males.

Lymph node ratio precisely predicts the benefit of postoperative radiotherapy in esophageal cancer: A retrospective cohort study.

BACKGROUND: The matter of postoperative radiotherapy (PORT) in esophageal cancer (ESCA) was far from conclusive. Some evidence indicated that lymph node status could affect treatment. We evaluated lymph node ratio (LNR) as an indicator that could be applied to predict PORT benefit. METHODS: Retrospective cohort study collected the data of N1, N2, N3 stage ESCA patients from the Surveillance, Epidemiology, and End Results database (SEER) to analyze the association between LNR and prognosis from 2004 to 2015. Patients were categorized into two subsets based on the LNR cut-off value of 0.23 using receiver operating characteristic curve (ROC). Kaplan-Meier analysis was utilized to estimate the proportion of overall survival (OS) and esophagus cancer-specific survival (CSS) in two LNR groups. Cox regression analysis and competitive risk model was adopted to investigate the impacts of LNR on prognosis. RESULTS: Of 2,165 ESCA patients identified, 1,165 (53.8%) had LNR>0.23. The LNR was an independent prognostic factor and associated with better OS and CSS of LNR≤0.23 (P < 0.001). In competitive risk model, a worse CSS was analyzed of LNR>0.23 (HR = 1.71; 95% CI 1.53-1.91). Subgroup analyses indicated that PORT was associated with favorable OS and CSS. Furthermore, when stratified by Node stage, PORT was associated with a survival benefit only in N1 stage with higher LNR (LNR>0.23) after adjusting for other covariates. CONCLUSIONS: LNR exceeding 0.23 was negatively associated with prognosis in ESCA. The survival benefit from PORT in ESCA seems to be limited to LNR of 23% or more only in N1 stage. This study highlights the biomarker meaning of LNR on identifying PORT beneficiary in N1 stage.

Dietary flavonoid intake is associated with a lower risk of diabetic nephropathy in US adults: data from NHANES 2007-2008, 2009-2010, and 2017-2018.

Few epidemiological studies have investigated the relationship between flavonoids and diabetic nephropathy (DN). Therefore, we explored the association between dietary flavonoid intake and DN among 1949 US adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2008, 2009-2010, and 2017-2018. Weighted logistic regression models demonstrated that the total flavonoid intake in the second (OR: 0.642; 95% CI: 0.456-0.906), third (OR: 0.665; 95% CI: 0.447-0.988), and the highest (OR: 0.551; 95% CI: 0.382-0.796) quantiles (versus the lowest) were associated with the decreased risk of DN. Restricted cubic spline (RCS) analyses showed that the total flavonoid intake had a negative linear association with DN (p-value for non-linearity was 0.003). Weighted quantile sum (WQS) regression analyses revealed that flavan-3-ols, flavones, and anthocyanidins were the main contributors for the combined effects of six flavonoid subclasses. Our findings suggested that higher dietary flavonoid intake was associated with a decreased risk of DN, with the greatest influence coming from flavan-3-ols, flavones, and anthocyanidins.

Associations of serum zinc, copper, and selenium with sleep disorders in the American adults: Data from NHANES 2011-2016.

BACKGROUND: Even though various studies have been conducted to investigate the relationship between trace metals and sleep, few epidemiological studies have evaluated the relationship between trace metals and sleep disorders in American adults. OBJECTIVE: This study intended to evaluate the associations of serum zinc (Zn), copper (Cu), selenium (Se), Zn/Cu, Zn/Se, and Cu/Se ratios with sleep disorders in American adults. METHODS: We conducted a cross-sectional analysis of 3660 adults aged ≥18 years old who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2016. Binary logistic regression was employed to calculate the odds ratio (OR) and 95 % confidence interval (CI) of either serum trace metals or serum trace metals ratios with risks among sleep disorder phenotypes. The restricted cubic spline (RCS) model was additionally utilized to check the dose-response relationships between serum trace metals, serum trace metals ratios, and sleep disorders. RESULTS: Logistic regression demonstrated that higher serum Zn (OR: 0.70, 95 % CI: 0.51-0.97, p = 0.035), Zn/Cu (OR: 0.62, 95 % CI: 0.45-0.87, p = 0.007), and Zn/Se (OR: 0.68, 95 % CI: 0.49-0.95, p = 0.025) were related to a decreased likelihood of self-reported sleep disorders, and dose-response relationships were detected by the RCS models, after adjustment for sociodemographic, behavioral, and health characteristics. No associations between serum Cu, Se, Cu/Se, and sleep disorders were observed. The findings in the sensitivity analyses were consistent with these results. CONCLUSION: Our study revealed that serum Zn, Zn/Cu, and Zn/Se were inversely associated with the risk of self-reported sleep disorders in US adults.

Physical activity, sedentary behavior, and the risk of type 2 diabetes: A two-sample Mendelian Randomization analysis in the European population.

Physical activity (PA) and sedentary behaviors (SB) have been linked to the risk of type 2 diabetes (T2DM) in observational studies; however, it is unclear whether these associations are causative or confounded. This study intends to use summary genetic data from the UK Biobank and other consortiums in conjunction with the two-sample Mendelian Randomization (MR) approach to solve this problem. The inverse variance weighted (IVW) technique was utilized as the primary analysis, with sensitivity analyses using the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Inverse associations between self-reported moderate PA (OR: 0.3096, 95% CI: 0.1782-0.5380) and vigorous PA (OR: 0.2747, 95% CI: 0.1390-0.5428) with T2DM risk were found, respectively. However, accelerometer-based PA measurement (average acceleration) was not associated with T2DM risk (OR: 1.0284, 95% CI: 0.9831-1.0758). The time (hours/day) spent watching TV was associated with T2DM risk (OR: 2.3490, 95% CI: 1.9084-2.8915), while the time (hours/day) spent using the computer (OR: 0.8496, 95% CI: 0.7178-1.0056), and driving (OR: 3.0679, 95% CI: 0.8448-11.1415) were not associated with T2DM risk. The sensitivity analysis revealed relationships of a similar magnitude. Our study revealed that more PA and less TV viewing were related to a decreased T2DM risk, and provided genetic support for a causal relationship between PA, TV viewing, and T2DM risk.

Relationship between dietary selenium intake and serum thyroid function measures in U.S. adults: Data from NHANES 2007-2012.

Although numerous studies have explored the relationship between selenium intake and thyroid diseases, few epidemiological studies have investigated the association between selenium intake and thyroid hormones. Therefore, we conducted this analysis to investigate the association between dietary selenium intake and thyroid hormones. Our sample included 5,575 adults (age ≥ 20) years from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Thyroid hormones, including total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), and thyroid-stimulating hormone (TSH), were detected. Multivariable linear regression models showed that log10-transformed selenium intake (LogSe) was negatively correlated with TT4 (ß = -0.383, 95% CI: -0.695, -0.070) and TT4/TT3 (ß = -0.003, 95% CI: -0.006, -0.0004) in U.S. adults. Besides, additional stratified analyses by sex demonstrated that LogSe was negatively associated with TT4 (ß = -0.007, 95% CI: -0.013, -0.001) and TT4/TT3 (ß = -0.664, 95% CI: -1.182, -0.146) and positively associated with FT4/TT4 (ß = 0.031, 95% CI: 0.004, 0.059) in male adults. Meanwhile, subgroup analysis by iodine status showed that LogSe was negatively associated with TT4 (ß = -0.006, 95% CI: -0.011, -0.002), FT4/FT3 (ß = -0.011, 95% CI: -0.023, -0.00002) and TT4/TT3 (ß = -0.456, 95% CI: -0.886, -0.026) in iodine sufficiency but not in iodine deficiency adults. Our results demonstrated that the increased dietary selenium intake was negatively correlated with TT4 and TT4/TT3 in U.S. adults. Furthermore, the association between dietary selenium intake and thyroid hormones was more pronounced in males and iodine sufficiency adults.

The causal impact of childhood obesity on bone mineral density and fracture in adulthood: A two-sample Mendelian randomization study.

Observational studies have indicated the associations between obesity with bone mineral density (BMD) and fracture but yield inconsistent results. The impact of childhood obesity on bone health in adulthood is even less clear. The present study adopted the Mendelian randomization methods to determine whether the genetically predicted childhood obesity was causally associated with BMD and the risk of fracture. Genetic variants were extracted from genome-wide association studies (GWAS) to identify childhood obesity loci [IEU open GWAS project: childhood obesity (ID: ieu-a-1096)] and single nucleotide polymorphisms (SNPs) as instrumental variables to investigate causality. We used two-sample univariable Mendelian randomization (MR) to estimate causal relationships between childhood obesity on BMD and fracture subtypes based on SNPs from European samples. To avoid bias, Cochran's Q test and leave-one-out variant analysis were performed. The MR analysis shows strong evidence that childhood obesity is causally associated with eBMD (OR 1.068, 95% CI 1.043-1.095, P < 0.001) and a weak decreased risk of leg fracture (OR 0.9990, 95% CI 0.9981-0.9999, P =0.033) based on the inverse variance weighting (IVW) method. After adjusting for diabetes and adult obesity, the results of eBMD remained the same. The MR analysis revealed sufficient evidence to indicate childhood obesity was causally associated with increased BMD and decreased risk of leg fracture in adults. Childhood obesity could be taken into consideration when assessing eBMD.

Genetic association between circulating selenium level and the risk of schizophrenia in the European population: A two-sample Mendelian randomization study.

Background: The association between circulating the selenium level and the risk of schizophrenia remains unclear. Objective: To determine the relationship between the circulating selenium level and the risk of schizophrenia, using the Mendelian Randomization method in the European population. Methods: Single nucleotide polymorphisms (SNPs) associated with the circulating selenium level were identified at p < 5 × 10-8. The inverse variance weighted (IVW) method was used as the principal MR analysis, and MR Egger, weighted median, and MR PRESSO were used to determine the accuracy of IVW results. The Cochran's Q-test and Leave-One-Out sensitivity analysis were performed to evaluate the heterogeneity and stability of genetic variants on schizophrenia. Results: The circulating selenium level was associated with decreased risk of schizophrenia by the IVW method (OR: 0.906, 95% CI:0.867-0.947). MR Egger, weighted median, and MR PRESSO methods got similar results. No heterogeneity was detected by the Cochran's Q-test, and no single SNP was driving the overall effect by leave-one-out analysis. Conclusion: Our study provides support for the genetic relationship between the circulating selenium level and schizophrenia; the decreased circulating selenium level was associated with an elevated risk of schizophrenia.

Higher HEI-2015 scores are associated with lower risk of gout and hyperuricemia: Results from the national health and nutrition examination survey 2007-2016.

Gout, the most prevalent inflammatory arthritis, is becoming increasingly prevalent in the United States and across the world, and it adversely impacts people's quality of life and their health. Few studies have focused on the relationship between daily dietary quality and gout, so the topic requires further exploration. Data were derived from the National Health and Nutrition Examination Survey 2007-2016, and the inclusion criteria of the analytic sample were (1) adults, age ≥20 years, with complete information about HEI-2015, gout, and uric acid; (2) complete information of demographics, lifestyle (BMI, smoking, drinking), and disease history [hypertension, chronic kidney disease (CKD), diabetes]. The quality of the daily diet was reflected using the Healthy Eating Index 2015 (HEI-2015). The baseline features of different groups were examined using the Scott-Rao chi-square tests, and the association between the HEI-2015 score and the risk of gout/hyperuricemia (HUA) was investigated using weighted logistic regression models. The effects of different dietary components in the HEI-2015 on reducing the risk of gout/HUA were evaluated by weighted quantile sum (WQS) regression models. After adjusting for demographic characteristics, behavioral covariates, and disease history, higher HEI-2015 scores were associated with a significantly lower risk of gout (OR: 0.878, 95% CI: 0.876-0.880) and HUA (OR: 0.978, 95% CI: 0.976-0.979) in weighted logistic regression. Dairy, whole grains, plant proteins, and added sugar contributed greatly in HEI-2015 to reducing gout risk (weights of WQS index: 42, 17.18, 16.13, and 7.93%, respectively). Dairy, total fruits, greens and beans, and plant proteins contributed greatly in HEI-2015 to reducing HUA risk (weights of WQS index: 28.9, 17.13, 16.84, and 11.39%, respectively). As the result, adherence to the American Dietary Guidelines may assist to decrease the risk of gout/HUA in American adults, and greater emphasis should be placed on dairy products, whole grains, fruits, legumes, and added sugars.

Higher HEI-2015 Scores Are Associated with Lower Risk of Sleep Disorder: Results from a Nationally Representative Survey of United States Adults.

Whether there is an association between dietary quality and sleep disorder in American adults is unclear. We conducted this study to analyze whether dietary quality, using the Healthy Eating Index-2015 (HEI-2015) scores as the measure, was associated with self-reported sleep disorders. Data came from the National Health and Nutrition Examination Survey (2005-2014). Step-weighted logistic regression models were performed to explore the relationships between the HEI-2015 scores and sleep disorder. Weighted quantile sum regression model was used to identify the HEI-2015 components most strongly associated with sleep disorders. According to quartiles, HEI scores were categorized into inadequate (<25%), average (25%-75%), and optimal (>75%). Compared to inadequate HEI status, average HEI status (OR: 0.961, 95%CI: 0.959-0.962) and optimal HEI status (OR: 0.913, 95% CI: 0.912-0.915) were associated with reduced risk of sleep disorder after multivariable adjustments. Greens and beans, added sugars, saturated fats, total vegetables and total protein foods were the top five important components for sleep disorders. Our results suggest that there is a statistically significant association between better dietary quality and reduced risk of sleep disorder among United States adults.

Urticaria and increased risk of rheumatoid arthritis: a two-sample Mendelian randomisation study in European population.

BACKGROUND: In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown. OBJECTIVE: To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach. METHODS: We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran's Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner. RESULTS: The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024-1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust. CONCLUSIONS: The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.