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Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

Background We examined the relationship between brain-derived neurotrophic factor (BDNF) and chronic kidney disease (CKD). Methods First, a cross-sectional study was conducted in 480 participants without known diabetes. An oral glucose tolerance test (OGTT) was administered after overnight fasting, and blood samples were collected at 0, 30, and 120 min. Second, a total of 3003 participants were enrolled for the case–control genetic analysis. After assigning them to a case or a control group based on age and CKD status, we investigated the association between BDNF gene variants and susceptibility to CKD. Results A higher fasting serum BDNF quartile was significantly associated with a lower prevalence of CKD (P value for trend Conclusions The BDNF level at fasting, but not at 30 and 120 min after glucose intake, was an independent indicator of CKD. In addition, significant associations were observed between three BDNF gene variants and CKD.

FORMOSAT-3/COSMIC (F3/C) constellation of six micro-satellites was launched into the circular low-earth orbit at 800 km altitude with a 72-degree inclination angle on 15 April 2006, uniformly monitoring the ionosphere by the GPS (Global Positioning System) Radio Occultation (RO). Each F3/C satellite is equipped with a TIP (Tiny Ionospheric Photometer) observing 135.6 nm emissions and a TBB (Tri-Band Beacon) for conducting ionospheric tomography. More than 2000 RO profiles per day for the first time allows us globally studying three-dimensional ionospheric electron density structures and formation mechanisms of the equatorial ionization anomaly, middle-latitude trough, Weddell/Okhotsk Sea anomaly, etc. In addition, several new findings, such as plasma caves, plasma depletion bays, etc., have been reported. F3/C electron density profiles together with ground-based GPS total electron contents can be used to monitor, nowcast, and forecast ionospheric space weather. The S4 index of GPS signal scintillations recorded by F3/C is useful for ionospheric irregularities monitoring as well as for positioning, navigation, and communication applications. F3/C was officially decommissioned on 1 May 2020 and replaced by FORMOSAT-7/COSMIC-2 (F7/C2). F7/C2 constellation of six small satellites was launched into the circular low-Earth orbit at 550 km altitude with a 24-degree inclination angle on 25 June 2019. F7/C2 carries an advanced TGRS (Tri Gnss (global navigation satellite system) Radio occultation System) instrument, which tracks more than 4000 RO profiles per day. Each F7/C2 satellite also has a RFB (Radio Reference Beacon) on board for ionospheric tomography and an IVM (Ion Velocity Meter) for measuring ion temperature, velocity, and density. F7/C2 TGRS, IVM, and RFB shall continue to expand the F3/C success in the ionospheric space weather forecasting.

An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses. We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data. Our meta-analysis identified 18 significant (p

Heme oxygenase (HO)-1 is a rate-limiting enzyme for degrading heme into carbon monoxide. Longer (GT)n repeat of the HO-1 gene (HMOX1) promoter has a lower transcription rate. Subjects with longer GT repeats in the HMOX1 promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) 30 repeats) (p

Most body mass index (BMI) genetic loci have been identified in studies of primarily European ancestries. The effect of these loci in other racial/ethnic groups is less clear. Thus, we aimed to characterize the generalizability of 170 established BMI variants, or their proxies, to diverse US populations and trans-ethnically fine-map 36 BMI loci using a sample of >102,000 adults of African, Hispanic/Latino, Asian, European and American Indian/Alaskan Native descent from the Population Architecture using Genomics and Epidemiology Study. We performed linear regression of the natural log of BMI (18.5-70kg/m2) on the additive single nucleotide polymorphisms (SNPs) at BMI loci on the MetaboChip (Illumina, Inc.), adjusting for age, sex, population stratification, study site, or relatedness. We then performed fixed-effect meta-analyses and a Bayesian trans-ethnic meta-analysis to empirically cluster by allele frequency differences. Finally, we approximated conditional and joint associations to test for the presence of secondary signals. We noted directional consistency with the previously reported risk alleles beyond what would have been expected by chance (binomial p&nbsp

The GPS radio occultation (RO) of FORMOSAT-3/COSMIC (F3/C) with 1–2.5-km-altitude resolution is used to scan fluctuations on vertical profiles of the ionospheric electron density induced by seismic and tsunami waves of the March 11, 2011 M9.0 Tohoku earthquake. The Hilbert–Huang transform is applied to derive the instantaneous wave number and amplitude of the fluctuations in 22 (7 before and 15 after) F3/C profiles within 3000 km in radius from the epicenter during the earthquake. Fluctuations of the vertical electron density profile induced by underneath Rayleigh and tsunami waves and their post-waves are examined. It is found that the right underneath Rayleigh wave can induce significant long-wavelength fluctuations of 50–105 km on the vertical profile of the electron density, while tsunami and their post-waves activate the prominent short-wavelength fluctuations less than 16 km on those profiles in the poleward side of the epicenter. Results show that RO is a powerful tool which is suitable to probe vertical fluctuations in the ionospheric electron density.

Night shift work is associated with cardiovascular disease and central nervous system disorders in female nurses. Brain-derived neurotrophic factor (BDNF) exerts protective effects on neural and endothelial functions. This study examined the association between serum BDNF levels and pulse pressure after rest in female nurses working night shifts. In this study, blood samples were collected for BDNF measurement after a night shift when nurses had been working night shifts for three continuous weeks. Blood pressure was assessed before and after a one-hour morning rest within a week of resuming the night shift after one month without any night shift work. The pulse pressure of nurses (n = 48, age 29 ± 5 years) was significantly reduced (from 43 ± 7 to 41 ± 6 mmHg, P = 0.003) after rest, and serum BDNF were significantly and inversely correlated with pulse pressure changes (r = −0.435, P = 0.002). Higher serum BDNF was an independent factor for greater reduction in pulse pressure (95%CI = −0.609 ‒ −0.174, P = 0.001). Using a receiver operating characteristic curve analysis, serum BDNF >20.6 ng/mL predicted a pulse pressure reduction after a one-hour rest (sensitivity 66.7%, specificity 77.8%). In conclusion, higher serum BDNF predicted greater recovery of pulse pressure after a one-hour rest in female nurses after night shift work.

Background There is a high hospitalization rate for diabetic patients. Since retinopathy and albuminuria are both important manifestations of microvascular disease in diabetes, our aim was to investigate the effect of retinopathy and albuminuria on long-term mortality in type 2 diabetic inpatients through this observational cohort study. Methods Type 2 diabetic inpatients given a primary diagnosis of poor glucose control were consecutively enrolled during their hospitalization periods. Clinical information was collected through review of each patient’s medical records, and mortality data were obtained from the national registry in Taiwan. Results A total of 761 type 2 diabetic inpatients were enrolled in the study with a median follow-up period of 6.6 years (interquartile range, 4.0–9.6 years). Patients in the Albuminuria(−)/Retinopathy(+), Albuminuria(+)/Retinopathy(−) and Albuminuria(+)/Retinopathy(+) groups had significantly higher risks of all-cause mortality and cardiovascular mortality than those in the Albuminuria(−)/Retinopathy(−) group. However, among patients with albuminuria, there was no significant difference in cumulative mortality between those with and without retinopathy (P = 0.821). A decrease in the estimated glomerular filtration rate (eGFR), but not retinopathy, was an independent predictor of all-cause mortality (95% CI 0.647‒0.893; P

Background It has been recognized that reduction of abdominal visceral fat and subcutaneous fat are associated with improvement in insulin-resistance (IR) after weight loss. However, few studies have investigated the correlation of reduction in epicardial adipose tissue (EAT) with improvement of IR index after weight loss in obese non-diabetic men with metabolic syndrome (MetS). Methods and results We prospectively enrolled 32 non-diabetic men with MetS for a 3-month weight reduction program mainly by diet control and exercise. Magnetic resonance imaging (MRI) examinations were used to measure EAT, subcutaneous fat, and abdominal visceral fat. Anthropometric parameters, oral glucose tolerance test (OGTT), and serum adipokines were assessed before and after the weight loss program. After a 3-month weight loss program, 27 obese MetS men had significant weight loss >5% (97 ± 14 to 87 ± 14 kg, with a 10.7 % decrease, p

Background This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. Methods Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-β, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index). Results At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p