Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry^1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis³, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach⁴, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry⁵. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Objectives: The present study was designed to evaluate effects of konjac glucomannan (KGM) supplement (3.6 g/day) for 28 days on blood lipid and glucose levels in hyperlipidemic type 2 diabetic patients and the possible mechanism for the reductions in blood lipid levels. Methods: Twenty-two diabetic subjects (age 64.2 + 8.4 years, BMI 25.5 + 3.2 kg/m²) with elevated blood cholesterol levels (fasting glucose between 6.7–14.4 mmol/L), but currently not taking lipid-lowering medication, were recruited to participate in a two 28-day period, randomized, double-blind, crossover clinical trial. Fasting blood samples drawn on the initial and final days of each period were determined for plasma lipids and glucose levels. Feces collected at the end of each experimental period were analyzed for neutral sterol and bile acid contents. Results: Compared with placebo, KGM effectively reduced plasma cholesterol (11.1%, p = 0.0001, adjusted α = 0.006), LDL-cholesterol (20.7%, p = 0.0004, adjusted α = 0.006), total/HDL cholesterol ratio (15.6%, p = 0.0005, adjusted α = 0.007), ApoB (12.9%, p = 0.0001, adjusted α = 0.006) and fasting glucose (23.2%, p = 0.002, adjusted α = 0.008). Plasma triglyceride, HDL-cholesterol, LDL/HDL cholesterol, postprandial glucose and body weight were not significant after adjustment by the Bonferroni-Hochberg procedure. Fecal neutral sterol and bile acid concentrations were increased by 18.0% (p = 0.004) and 75.4% (p < 0.001), respectively, with KGM supplement. Conclusions: The KGM supplement improved blood lipid levels by enhancing fecal excretion of neutral sterol and bile acid and alleviated the elevated glucose levels in diabetic subjects. KGM could be an adjunct for the treatment of hyperlipidemic diabetic subjects.

Background: Cervical cancer is the most common cancer experienced by women worldwide; however, screening techniques are very effective for reducing the risk of death. The national cervical cancer screening program was implemented in Taiwan in 1995. The objective of this study was to examine and provide evidence of the cervical cancer mortality trends for the periods before and after the screening program was implemented. Methods: Data from 1981 to 2010 of the causes of death registered were obtained from the Department of Health, Taiwan. Age-standardized mortality rates, age-specific rates, and age-period-cohort models that employed the sequential method were used to assess temporal changes that occurred between 1981 and 2010, with 1995 used as the separating year. Results: The results showed that for both time periods of 1981 to 1995 and 1996 to 2010, age and period had significant effects, whereas the birth cohort effects were insignificant. For patients between 80 and 84 years of age, the mortality rate for 1981 to 1995 and 1996 to 2010 was 48.34 and 68.08. The cervical cancer mortality rate for 1996 to 2010 was 1.0 for patients between 75 and 79 years of age and 1.4 for patients between 80 and 84 years of age compared to that for 1981 to 1995. Regarding the period effect, the mortality trend decreased 2-fold from 1996 to 2010. Conclusions: The results of this study indicate a decline in cervical cancer mortality trends after the screening program involving Papanicolaou tests was implemented in 1995. However, the positive effects of the screening program were not observed in elderly women because of treatment delays during the initial implementation of the screening program.

The aim of this study was to investigate the association between fine particulate matter 2.5 (PM_2.5) and oral cancer among Taiwanese men. Four linked data sources including the Taiwan Cancer Registry, Adult Preventive Medical Services Database, National Health Insurance Research Database, and Air Quality Monitoring Database were used. Concentrations of sulfur dioxide, carbon monoxide, ozone, NOx (nitrogen monoxide and nitrogen dioxide), coarse particulate matter (PM_10-2.5) and PM_2.5 in 2009 were assessed in quartiles. A total of 482 659 men aged 40 years and above were included in the analysis. Logistic regression was used to examine the association between PM_2.5 and oral cancer diagnosed from 2012 to 2013. After adjusting for potential confounders, the ORs of oral cancer were 0.91 (95% CI 0.75 to 1.11) for 26.74≤PM_2.5<32.37, 1.01 (95% CI 0.84 to 1.20) for 32.37≤PM_2.5<40.37 μg/m³ and 1.43 (95% CI 1.17 to 1.74) for PM_2.5≥40.37 μg/m³ compared with PM_2.5<26.74 μg/m³. In this study, there was an increased risk of oral cancer among Taiwanese men who were exposed to higher concentrations of PM_2.5.