BACKGROUND: In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries. METHODS: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals. RESULTS: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences. CONCLUSIONS: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings.
- MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- dítě MeSH
- konsensus MeSH
- lidé MeSH
- připravenost na pandemii * MeSH
- výzkumný projekt MeSH
- zdraví dítěte MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.
- MeSH
- androgeny * genetika MeSH
- celogenomová asociační studie * MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- ledviny MeSH
- lidé MeSH
- lidské chromozomy X genetika MeSH
- responzivní elementy MeSH
- tetraspaniny genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Learning from the COVID-19 pandemic and considering the effects of this pandemic, we provide recommendations that can guide towards sustainable RSV surveillance with the potential to be integrated into the broader perspective of respiratory surveillance. https://bit.ly/40TsO0G
Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infections and hospitalisations among young children and is globally responsible for many deaths in young children, especially in infants aged <6 months. Furthermore, RSV is a common cause of severe respiratory disease and hospitalisation among older adults. The development of new candidate vaccines and monoclonal antibodies highlights the need for reliable surveillance of RSV. In the European Union (EU), no up-to-date general recommendations on RSV surveillance are currently available. Based on outcomes of a workshop with 29 European experts in the field of RSV virology, epidemiology and public health, we provide recommendations for developing a feasible and sustainable national surveillance strategy for RSV that will enable harmonisation and data comparison at the European level. We discuss three surveillance components: active sentinel community surveillance, active sentinel hospital surveillance and passive laboratory surveillance, using the EU acute respiratory infection and World Health Organization (WHO) extended severe acute respiratory infection case definitions. Furthermore, we recommend the use of quantitative reverse transcriptase PCR-based assays as the standard detection method for RSV and virus genetic characterisation, if possible, to monitor genetic evolution. These guidelines provide a basis for good quality, feasible and affordable surveillance of RSV. Harmonisation of surveillance standards at the European and global level will contribute to the wider availability of national level RSV surveillance data for regional and global analysis, and for estimation of RSV burden and the impact of future immunisation programmes.
- MeSH
- dítě MeSH
- hospitalizace MeSH
- infekce dýchací soustavy * diagnóza epidemiologie MeSH
- infekce respiračními syncytiálními viry * diagnóza epidemiologie prevence a kontrola MeSH
- kojenec MeSH
- lidé MeSH
- lidský respirační syncytiální virus * MeSH
- předškolní dítě MeSH
- senioři MeSH
- sentinelová surveillance MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
- MeSH
- alely MeSH
- celogenomová asociační studie MeSH
- checkpoint kinasa 1 genetika MeSH
- checkpoint kinasa 2 genetika MeSH
- diabetes mellitus 2. typu MeSH
- dieta MeSH
- dlouhověkost genetika MeSH
- dospělí MeSH
- fertilita genetika MeSH
- genetická predispozice k nemoci MeSH
- kosti a kostní tkáň metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- menopauza genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- ovarium metabolismus MeSH
- předčasná menopauza genetika MeSH
- primární ovariální insuficience genetika MeSH
- protein FMRP genetika MeSH
- stárnutí genetika MeSH
- uterus MeSH
- zdravé stárnutí genetika MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Dálný východ MeSH
- Evropa MeSH
Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
- MeSH
- ABC transportér z rodiny G, člen 2 genetika MeSH
- celogenomová asociační studie MeSH
- dna (nemoc) krev epidemiologie genetika MeSH
- genetická predispozice k nemoci MeSH
- genetické lokusy MeSH
- genetické markery * MeSH
- hepatocytární jaderný faktor 1-alfa genetika MeSH
- hepatocytární jaderný faktor 4 genetika MeSH
- játra metabolismus patologie MeSH
- jednonukleotidový polymorfismus * MeSH
- kardiovaskulární nemoci krev epidemiologie genetika MeSH
- kohortové studie MeSH
- kyselina močová krev MeSH
- ledviny metabolismus patologie MeSH
- lidé MeSH
- metabolické nemoci krev epidemiologie genetika MeSH
- nádorové proteiny genetika MeSH
- orgánová specificita MeSH
- signální transdukce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
- MeSH
- běloši MeSH
- celogenomová asociační studie MeSH
- chronická renální insuficience genetika patofyziologie moč MeSH
- fenotyp MeSH
- genetická predispozice k nemoci * MeSH
- genetické asociační studie metody MeSH
- hodnoty glomerulární filtrace MeSH
- jednonukleotidový polymorfismus MeSH
- kvantitativní znak dědičný * MeSH
- lidé MeSH
- lokus kvantitativního znaku * MeSH
- mapování chromozomů MeSH
- typy dědičnosti MeSH
- uromodulin moč MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
- MeSH
- celogenomová asociační studie metody MeSH
- dospělí MeSH
- elektrokardiografie metody MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard metabolismus MeSH
- náhlá srdeční smrt etiologie MeSH
- senioři MeSH
- srdeční arytmie genetika metabolismus MeSH
- srdeční komory metabolismus MeSH
- syndrom dlouhého QT genetika metabolismus MeSH
- vápníková signalizace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
