Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.
Recent studies have shown that inconsistent results of safety and efficacy between sonothombolysis vs. non-sonothombolysis in acute ischemic stroke (AIS). We implemented a meta-analysis to explore the value of sonothrombolysis in AIS treatment. The MEDLINE, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) which had evaluated sonothrombolysis or ultrasound thrombolysis in AIS. One hundred five studies were retrieved and analyzed, among them, 7 RCTs were included in the current meta-analysis. In comparison with the non-sonothombolysis, sonothrombolysis significantly improved complete recanalization (RR 2.16, 95% CI 1.51 to 3.08, P < 0.001), complete or partial recanalization (RR 1.90, 95% CI 1.26 to 2.88, P = 0.002), there is also a tendency to improvement of ≥ 4 points in NIHSS score (RR 1.43, 95% CI 0.99 to 2.07, P = 0.057). However, sonothrombolysis and non-sonothrombolysis had insignificant differences in neurological recovery and adverse events. In subgroup analysis, we found that “With t-PA”, “NIHSS > 15”, “Treatment time ≤ 150min”, and “Age ≤ 65 years” are potential favorable factors for efficacy outcomes of sonothombolysis. Sonothrombolysis can significantly increase the rate of recanalization in patients with AIS compared with non-sonothrombolysis, but there is no significant effect on improving neurological functional recovery and avoiding complications.
A cross-sectional study to show whether and how serum fasting homocysteine levels are associated with renal function changes in patients with hypertension. Homocysteine levels were associated with serum creatinine and blood urea nitrogen (BUN) levels with coefficients of 2.04 and 0.07, respectively, only in males and independent of confounders. In addition, low density lipoprotein cholesterol (LDL-C) levels were positively and left ventricular ejection fraction (LVEF) was negatively associated with serum creatinine level in males; age was positively associated with serum creatinine levels in females. Age was a common risk factor positively associated with BUN levels in both sexes, while total cholesterol (TC) levels and glycemic control were independent risk factors that were positively associated with BUN levels only in males. LDL-C levels and LVEF were negatively associated with BUN levels in females. Body mass index (BMI) was positively associated and hemoglobin A1c (HbA1c) levels, high density lipoprotein cholesterol (HDL-C) levels and the presence of stroke were negatively associated with serum uric acid levels in male patients. In contrast, only LVEF was positively associated with uric acid levels in females. In conclusion, homocysteine level is an independent risk factor associated with serum creatinine and BUN levels in male patients with hypertension.
We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.
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