| 1. |
- Mishra, A., et al.
(författare)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Tidskriftsartikel (refereegranskat)abstract
- 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 analysis(3), 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 approach(4), 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 ancestry(5). 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.
|
|
| 2. |
- Amouzou, A, et al.
(författare)
-
Health service utilisation during the COVID-19 pandemic in sub-Saharan Africa in 2020: a multicountry empirical assessment with a focus on maternal, newborn and child health services
- 2022
-
Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 7:5
-
Tidskriftsartikel (refereegranskat)abstract
- There are concerns about the impact of the COVID-19 pandemic on the continuation of essential health services in sub-Saharan Africa. Through the Countdown to 2030 for Women’s, Children’s and Adolescents’ Health country collaborations, analysts from country and global public health institutions and ministries of health assessed the trends in selected services for maternal, newborn and child health, general service utilisation.MethodsMonthly routine health facility data by district for the period 2017–2020 were compiled by 12 country teams and adjusted after extensive quality assessments. Mixed effects linear regressions were used to estimate the size of any change in service utilisation for each month from March to December 2020 and for the whole COVID-19 period in 2020.ResultsThe completeness of reporting of health facilities was high in 2020 (median of 12 countries, 96% national and 91% of districts ≥90%), higher than in the preceding years and extreme outliers were few. The country median reduction in utilisation of nine health services for the whole period March–December 2020 was 3.9% (range: −8.2 to 2.4). The greatest reductions were observed for inpatient admissions (median=−17.0%) and outpatient admissions (median=−7.1%), while antenatal, delivery care and immunisation services generally had smaller reductions (median from −2% to −6%). Eastern African countries had greater reductions than those in West Africa, and rural districts were slightly more affected than urban districts. The greatest drop in services was observed for March–June 2020 for general services, when the response was strongest as measured by a stringency index.ConclusionThe district health facility reports provide a solid basis for trend assessment after extensive data quality assessment and adjustment. Even the modest negative impact on service utilisation observed in most countries will require major efforts, supported by the international partners, to maintain progress towards the SDG health targets by 2030.
|
|
