SEARCH · PubMed Health

Results for “demographic inference”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

34 records · Page 2Linked to original sources

PubMed2025

Sex-biased Migration and Demographic History of the Big European Firefly Lampyris noctiluca.

Differential dispersion between the sexes can impact the colonization process and demographic history of a species. Here, we explored the demographic history of the big European firefly, Lampyris noctiluca, which exhibits female neoteny. Distribution of L. noctiluca extends throughout Europe, but nothing is known about its colonization process. To investigate its demographic history, we produced the first Lampyris genome (653 Mb), including an IsoSeq annotation and the identification of the X chromosome. We collected 115 individuals from six populations of L. noctiluca (Finland to Italy) and generated whole-genome re-sequencing data for each individual. We inferred several population expansions and bottlenecks throughout the Pleistocene that correlate with glaciation events. Surprisingly, we uncovered strong population structure and low gene flow. We reject a stepwise, south to north, colonization history scenario and instead uncovered a complex demographic history with a putative eastern European origin. Analyzing the evolutionary history of the mitochondrial genome as well as X-linked and autosomal loci, we found evidence of a maternal colonialization of Germany, putatively from a farther western European population, followed by a male-only migration from south of the Alps (Italy). Overall, investigating the demographic history and colonization patterns of a species should form part of an integrative approach of biodiversity research. Our results provide evidence of sex-biased migration which is important to consider for demographic, biogeographic and species delimitation studies.

Animals↗

PubMed2025

Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity.

IMPORTANCE: Understanding the pathogenic mechanisms of Fuchs endothelial corneal dystrophy (FECD) could contribute to developing gene-targeted therapies. OBJECTIVE: To investigate associations between demographic data and age at first keratoplasty in a genetically refined FECD cohort. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study recruited 894 individuals with FECD at Moorfields Eye Hospital (London) and General University Hospital (Prague) from September 2009 to July 2023. Ancestry was inferred from genome-wide single nucleotide polymorphism array data. CTG18.1 status was determined by short tandem repeat and/or triplet-primed polymerase chain reaction. One or more expanded alleles (≥50 repeats) were classified as expansion-positive (Exp+). Expansion-negative (Exp-) cases were exome sequenced. MAIN OUTCOMES AND MEASURES: Association between variants in FECD-associated genes, demographic data, and age at first keratoplasty. RESULTS: Within the total cohort (n = 894), 77.3% of patients were Exp+. Most European (668 of 829 [80.6%]) and South Asian (14 of 22 [63.6%]) patients were Exp+. The percentage of female patients was higher (151 [74.4%]) in the Exp- cohort compared to the Exp+ cohort (395 [57.2%]; difference, 17.2%; 95% CI, 10.1%-24.3%; P < .001). The median (IQR) age at first keratoplasty of the Exp + patients (68.2 years [63.2-73.6]) was older than the Exp- patients (61.3 years [52.6-70.4]; difference, 6.5 years; 95% CI, 3.4-9.7; P < .001). The CTG18.1 repeat length of the largest expanded allele within the Exp+ group was inversely correlated with the age at first keratoplasty (β, -0.087; 95% CI, -0.162 to -0.012; P = .02). The ratio of biallelic to monoallelic expanded alleles was higher in the FECD cohort (1:14) compared to an unaffected control group (1:94; P < .001), indicating that 2 Exp+ alleles were associated with increased disease penetrance compared with 1 expansion. Potentially pathogenic variants (minor allele frequency, <0.01; combined annotation dependent depletion, >15) were only identified in FECD-associated genes in 13 Exp- individuals (10.1%). CONCLUSIONS AND RELEVANCE: In this multicenter cohort study among individuals with FECD, CTG18.1 expansions were present in most European and South Asian patients, while CTG18.1 repeat length and zygosity status were associated with modifications in disease severity and penetrance. Known disease-associated genes accounted for only a minority of Exp- cases, with unknown risk factors associated with disease in the rest of this subgroup. These data may have implications for future FECD gene-targeted therapy development.

Adult↗

PubMedDate not supplied

Anxious symptomatic volunteers in the Twin Cities: sociodemographic description and MMPI psychodiagnosis.

This paper underscores the need for true sample selection before statistical inference of any value can be made. Its findings suggest that the sample selection strategy of symptomatic volunteers can produce samples of anxious subjects with remarkable demographic similarity across the country. Anxiety as a constitutional rather than pathognomonic symptom is illustrated by the heterogeneity of its psychometric evaluation in our volunteers. Expecting a drug to safely relieve the anxiety of all anxious symptomatic volunteers is akin to expecting a drug to safely relieve the headaches of all headache sufferers. We feel that careful psychodiagnosis remains the best sample selection strategy.

Adolescent↗

PubMed2026

Adaptation to seasonal drought in Arabis alpina is linked to the demographic history and climatic changes since the last glacial maximum.

Understanding how species adapt to new environments is a central goal in evolutionary biology, and a topical question in climate change research. Here, we sequenced the genomes of 426 individuals of the perennial, Arctic-alpine herb Arabis alpina to study demography and adaptation, with a focus on populations in Northern Spain, that experience warm and dry summers. Our inference supports a scenario in which A. alpina colonized Northern Spain in a range expansion event that started near the Alps around 216 thousand years ago (kya). During the last glacial episode (115 to 12 kya), this expansion proceeded westward, and effective population sizes were large across Europe, likely due to a larger suitable habitat for A. alpina. These ancient demographic events gave rise to a highly diverged genetic lineage in Northern Spain. In the present interglacial (between 12 kya and present), populations became increasingly fragmented, and lost genetic diversity across Europe. Furthermore, we detected signatures of selection at genes associated with responses to abiotic stress, including drought stress, and regulation of growth, for instance at SC5D and NAC055, which reflects the climatic changes since the last glacial period. Notably, an ancient polymorphism at the gene FRL1 emerged as a candidate for conferring variation in flowering behavior, and for contributing to adaptation to drought. Our study suggests that the combination of ancestral variation in flowering behavior, and positive selection on new mutations involved in drought responses, underlies the evolution of a new trait syndrome, and adaptation to climate change.

Droughts↗

PubMed2025

Efficient Detection and Characterization of Targets of Natural Selection Using Transfer Learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pretrained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Selection, Genetic↗

PubMed2025

Efficient detection and characterization of targets of natural selection using transfer learning.

Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pre-trained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.

Journal Article↗

PubMed2026

Comparative Population Genomics of Relictual Caribbean Island Gossypium hirsutum.

Gossypium hirsutum is the world's most important source of cotton fibre, yet the diversity and population structure of its wild forms remain largely unexplored. The complex domestication history of G. hirsutum combined with reciprocal introgression with a second domesticated species, G. barbadense, has generated a wealth of morphological forms and feral derivatives of both species and their interspecies recombinants, which collectively are scattered across a large geographic range in arid regions of the Caribbean basin. Here we assessed genetic diversity within and among populations from two Caribbean islands, Puerto Rico (n = 43, five sites) and Guadeloupe (n = 25, one site), which contain putative wild or introgressed forms. Using whole-genome resequencing data and a phylogenomic framework derived from a broader genomic survey, we parsed individuals into feral derivatives and truly wild forms. Feral cottons display uneven levels of genetic and morphological resemblance to domesticated cottons, with diverse patterns of genetic variation and heterozygosity. These patterns are inferred to reflect a complex history of interspecific and intraspecific gene flow that is spatially highly variable in its effects. Wild cottons in both Caribbean islands appear to be relatively inbred, especially the Guadeloupe samples. Our results highlight the dynamics of population demographics in relictual wild cottons that experienced profound genetic bottlenecks associated with repeated habitat destruction superimposed on a natural ecogeographical distribution comprising widely scattered populations. These results have implications for conservation and utilisation of wild diversity in G. hirsutum.

Genetics, Population↗

PubMed2025

Invasive Streptococcus dysgalactiae subspecies equisimilis compared with Streptococcus pyogenes in Australia, 2011-23, and the emergence of a multi-continent stG62647 lineage: a retrospective clinical and genomic epidemiology study.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is closely related to Streptococcus pyogenes, with overlapping disease manifestations. We compared the clinical and genomic epidemiology of invasive SDSE with invasive S pyogenes across different settings in Australia and phylogenetically contextualised the SDSE sequences within a global cohort of genomes. METHODS: In this retrospective clinical and genomic epidemiology study, cases of invasive SDSE isolated from normally sterile sites were identified and whole-genome sequenced across five hospital networks in temperate southeast Australia (Melbourne and Sydney) and the tropical Top End of the Northern Territory. SDSE disease incidence, case demographics, clinical outcomes, and longitudinal lineage dynamics were compared between southeast Australia and the Top End and to co-collected invasive S pyogenes cases in each region. SDSE genomes and lineages were also contextualised within 1166 global SDSE sequences. Genomic transmission clusters (not necessarily direct transmission) were inferred between isolates from different individuals by single-linkage clustering at a single nucleotide polymorphism threshold of less than or equal to seven for SDSE and less than or equal to five for S pyogenes based on previous transmission analyses. FINDINGS: Between Jan 1, 2011, and Feb 28, 2023, there were 693 invasive SDSE cases and 995 invasive S pyogenes cases. Invasive SDSE occurred almost exclusively in adults. The overall invasive SDSE incidence in southeast Australia was similar to invasive S pyogenes (incidence rate ratio [IRR] 1·15, 95% CI 0·91-1·46; p=0·26) and increased over the study period (IRR 1·06 per year, 95% CI 1·05-1·08; p<0·0001) from 1·30 cases per 10 000 admissions in 2011 to 3·72 cases per 10 000 admissions in the first 2 months of 2023 (95% CI 2·13-6·07). In southeast Australia, where stringent COVID-19 non-pharmaceutical interventions (NPIs) were implemented between 2020 and 2021, the SDSE incidence plateaued during 2020-21 but did not significantly decline (IRR 1·09 compared with 2017-19, 95% CI 0·88-1·35; p=0·47). By contrast, S pyogenes incidence substantially declined in 2020-21 in southeast Australia (IRR 0·35 compared to 2017-19, 95% CI 0·22-0·52; p=0·017). In the Top End, SDSE incidence was lower than S pyogenes (IRR 0·24, 95% CI 0·19-0·31; p<0·0001). However, crude incidence remained higher than southeast Australia (crude IRR 1·24, 95% CI 1·07-1·42; p=0·0037) and disproportionately affected First Nations Australians in the Top End compared with non-First Nations individuals (IRR 3·36, 95% CI 2·33-4·85; p<0·0001). Comparing 2020-21 with 2017-19, there was no decline in SDSE (IRR 1·27, 95% CI 0·73-2·24; p=0·45) or S pyogenes (IRR 0·97, 95% CI 0·80-1·18; p=0·81) incidence in the Top End, which did not implement prolonged stringent COVID-19 NPIs. Analysing the available genomes of invasive cases and in lineages for which more than or equal to five invasive cases occurred, only 24 (6%) of 384 SDSE cases were assigned to genomic transmission clusters, compared with 271 (52%) of 524 S pyogenes cases. An stG62647 lineage encompassed 113 (26%) of 436 sequenced SDSE genomes. Analysis of available SDSE sequences from Australia, western Europe, and North America inferred concurrent international expansion of the stG62647 lineage in all three regions between 1990 and 2005. INTERPRETATION: We identified a substantial burden of invasive SDSE, dominated by the emergent stG62647 lineage. The contrasting epidemiology between species in the different Australian regions, during COVID-19 NPIs, and genomic infection patterns indicates transmission dynamic, pathogen population, and host-pathogen interaction differences between SDSE and S pyogenes and indicates implications for disease control measures. FUNDING: Australian National Health and Medical Research Council.

Humans↗

PubMed2025

Nested Admixture During and After the Trans-Atlantic Slave Trade on the Island of São Tomé.

Human genetic admixture, involving the contact between two or more previously isolated populations, can be a complex process influenced by social dynamics. In this study, we aim to reconstruct complex admixture histories in São Tomé, an island in the Gulf of Guinea where the Portuguese established one of the first plantation-based slave societies. Since the 15th century, migration waves from Africa and Europe, slavery, marooning, and indentured labour led to profound demographic shifts and social stratification on the island. Examining 2.5 million SNPs newly genotyped in 96 São Toméans, we observed patterns of genetic differentiation that were more complex than those of other populations descended from enslaved Africans on either side of the Atlantic. Using local ancestry inference and Identical-by-Descent methods, we identified five genetic clusters in São Tomé and reconstructed shared ancestries between each cluster and 70 African and European population samples, including an extensive sample from the Cabo Verde archipelago. Our findings align with historical records, retracing the major slave trade routes and labour-driven migrations after the abolition of slavery. We also identified gene flow between recently admixed groups that were previously isolated on the island. We call this process, creating multiple layers of genetic ancestry in admixed genomes, nested admixture. We suggest that changing social structures in São Tomé transformed the genetic structure of its population and influenced the admixture process. This study demonstrates how successive admixture and isolation events during and after the Trans-Atlantic Slave Trade shaped extant genetic diversity patterns at local scale in Africa.

Humans↗

PubMed1977

Colorectal cancer and beer drinking.

Evidence is presented of a significant statistical association between beer drinking and colorectal cancer, particularly rectal cancer. This finding is based on correlations between consumption and cancer mortality and between changes in consumption and changes in cancer mortality for 47 states in the United States of America. Also various secular trends, an urban-rural gradient, socioeconomic gradients and sex ratios in the United States are shown to be generally consistent with a relationship between beer consumption and colorectal cancer, particularly rectal cancer. The limitations on drawing sound aetiological inferences from such data are acknowledged. In particular, several other variables are shown to be associated with both beer drinking and colorectal cancer. Also, a discussion of previous epidemiological studies is given, and it appears there is only a limited amount of direct evidence in humans to support the statistical demographic relationships.

Alcohol Drinking↗

PubMed2026

Lineage-specific transmission and spatial clustering of Mycobacterium tuberculosis in Kaohsiung, Taiwan, in 2019-23: a population-based genomic study.

BACKGROUND: The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS: In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS: During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86·7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84·8%) isolates. 1219 (29·2%) of 4168 individuals were female and 2947 (70·7%) were male; the median age was 69·7 years (IQR 57·4-80·7). The dominant lineages were lineage 1 (1749 [42·0%] of 4168 isolates), lineage 2 (1510 [36·2%]), and lineage 4 (905 [21·7%]). 1069 (25·6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2·15 [95% CI 1·80-2·52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2·75 [1·16-6·89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5·64 [4·16-7·68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50·8% of all transmission events. INTERPRETATION: This sequencing study revealed that older adults (aged ≥65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING: Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.

Mycobacterium tuberculosis↗

PubMed2026

Comparison of phylogenetic metrics of transmission between symptomatic and asymptomatic tuberculosis in individuals who were incarcerated in Brazil in 2008-24: a retrospective genomic epidemiology study.

BACKGROUND: Tuberculosis control efforts have traditionally targeted symptomatic individuals; however, the role of asymptomatic cases in sustaining transmission is increasingly recognised. We aimed to quantify the contribution of asymptomatic tuberculosis to recent transmission using genomic and epidemiological data from a high-transmission setting. METHODS: We conducted a retrospective genomic epidemiology study of Mycobacterium tuberculosis isolates collected in Mato Grosso do Sul, Brazil, between Aug 25, 2008, and March 19, 2024. Available isolates underwent whole-genome sequencing. Demographic, clinical, incarceration history, and laboratory metadata were obtained from surveillance records. From Jan 1, 2017, to March 19, 2024, active case finding was conducted in the state's three largest prisons (all male-only facilities), during which sputum samples were collected from individuals irrespective of symptoms and tested using GeneXpert and culture. Comparisons of transmission between individuals with and without symptoms were restricted to individuals who were incarcerated and were identified through active case finding and for whom high-quality, M tuberculosis lineage 4 genomes were available. Metrics of recent transmission included phylogenetic clustering, time-scaled haplotype density (THD), local branching index (LBI), and transmission probabilities inferred using Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories. FINDINGS: 4448 tuberculosis cases were notified in Mato Grosso do Sul in 2008-24. After excluding cases for which M tuberculosis isolates were not available or had low sequencing quality, who had contaminated cultures or mixed infection, or who were infected with non-lineage 4 M tuberculosis, we included 2362 lineage 4 M tuberculosis isolates with high-quality genome sequences. 1849 (78·3%) of 2362 isolates were part of a genomic cluster. Among 2362 individuals with tuberculosis, 1137 (48·1%) were incarcerated at diagnosis. Of these individuals, 505 were identified through active case finding in three male-only prisons. The median age was 30 years (IQR 25-37); 304 (60·2%) had mixed ethnicity, 90 (17·8%) were White, 56 (11·1%) were Black, 13 (2·6%) were Indigenous, and six (1·2%) were Asian. 277 (54·9%) had symptomatic disease and 228 (45·1%) had asymptomatic tuberculosis. There were no significant differences between symptomatic and asymptomatic individuals in phylogenetic clustering (213 [76·9%] of 277 vs 195 [85·5%] of 228; p=0·37), THD (median 0·39 [IQR 0·06-0·62] vs 0·50 [0·09-0·65]; p=0·12), or LBI (0·00863 [0·00810-0·00988] vs 0·00871 [0·00829-0·01020]; p=0·088). Bayesian transmission trees showed no significant difference in the number of secondary infections inferred from symptomatic compared with asymptomatic individuals (p=0·56). These findings were consistent across genomic clusters and robust to model assumptions. INTERPRETATION: We identified no differences in transmission between individuals who were symptomatic and those who were asymptomatic using multiple genomic measures. In this high-transmission setting, where systematic screening is implemented, our findings indicate that asymptomatic tuberculosis substantially contributes to tuberculosis transmission at the population level. These results suggest that symptom-based case detection alone is likely to be insufficient to interrupt transmission and highlight the importance of expanded screening strategies in high-risk populations. FUNDING: US National Institutes of Health and the Brazilian National Research Council (CNPq).

Humans↗

PubMed2025

Genomic analysis of xerophyte Salweenia species provides insights into the alpine dry-warm valleys divergence and survival history.

Salweenia species are evergreen shrubs capable of preventing desertification and maintaining the health of alpine dry-warm ecosystems in the Hengduan Mountains. However, both the narrowly distributed S. bouffordiana and its more widespread close relative S. wardii are endemic and endangered. Furthermore, their small population sizes render each of these species at risk of extinction. To infer how past climate changes have shaped the evolutionary history of these species, we developed a chromosome-level S. bouffordiana genome (788 Mb) and compared the two species' evolutionary histories, genetic loads and the genomic adaptions to local environmental conditions using whole-genome resequencing data. Our findings reveal a sharp population decline from the Pliocene to the Quaternary. However, populations of S. bouffordiana then started to recover before declining further, while S. wardii populations continued to decline until recently. Abundant homozygous-derived variants accumulated in the two species, particularly in S. bouffordiana, while the species with the most heterozygous variants was S. wardii. Accumulated extensive inbreeding effects but possessed few LOF mutations and few highly deleterious variants in the S. bouffordiana that have experienced the most severe demographic bottlenecks, most likely because of purging effects. This accelerating decline cascade will likely be detrimental to the consequences for the species' future viability and adaptive potential. Overall, this study improves our understanding of the evolutionary history of Salweenia shrubs tolerant to extreme environments and offers a genetic resource for future breeding and conservation efforts.

Genome, Plant↗

PubMed2026

Incidence patterns and genetic validation of primary glaucoma subtypes among 1 million adults in China and the UK.

BACKGROUND/AIMS: Primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) are distinct diseases, yet many glaucoma cases in population-based datasets lack subtype specification. We assessed incidence patterns of glaucoma subtypes in China and the UK and used genetic evidence to infer the likely subtype composition of cases recorded as unspecified glaucoma. METHODS: Incident primary glaucoma was identified from linked inpatient records in the prospective China Kadoorie Biobank (CKB; n=512 504) and UK Biobank (UKB; n=492 329) studies. Cohort-specific phenotyping algorithms defined POAG, PACG and unspecified glaucoma. Adjusted incidence rates were estimated by direct standardisation. To support subtype inference, polygenic risk scores (PRSs) were constructed using ancestry-specific genome-wide association studies, including a new East Asian PACG meta-analysis, and tested for association with glaucoma phenotypes using multivariable logistic regression. RESULTS: Over 12 years of follow-up, 1658 primary glaucoma cases were identified in CKB and 7643 in UKB. Most (>68%) cases lacked subtype specification. Incidence increased with age and was twofold higher among women for PACG in both cohorts and for unspecified glaucoma in CKB. In UKB, POAG incidence was fivefold higher among Black than White participants, with a similar but attenuated pattern for unspecified glaucoma. PRS analyses indicated that unspecified glaucoma closely aligned with PACG in CKB but was more heterogeneous in UKB. CONCLUSION: Healthcare-recorded incidence patterns for POAG and PACG were consistent with established demographic risk factors, whereas unspecified glaucoma showed differences in subtype composition between populations. Integrating epidemiological and genetic evidence improves interpretation of glaucoma phenotypes when detailed clinical information is unavailable.

Epidemiology↗

PubMed2026

Exploring China's Clean Air Act and associated cardiovascular disease risk: a prospective, quasi-experimental, and causal inference modelling study.

BACKGROUND: Substantial improvements in air quality have been recorded following the implementation of China's Clean Air Act (CCAA) in 2013. However, the association between CCAA implementation and individual-level cardiovascular disease (CVD) risk remains unclear. We aimed to examine the long-term association between CCAA implementation and individual-level predicted CVD risk. METHODS: In this prospective, quasi-experimental study, we used data from the China Kadoorie Biobank, a prospective cohort study that recruited participants from five urban and five rural areas across China between 2004 and 2008, with three resurveys conducted after the baseline survey (in 2008, 2013-14, and 2020-21). We included 34 862 individuals (mean age 51·3 years) who participated in at least one resurvey and had no history of CVD at baseline. Participants were classified into intervention (n=25 497) and control (n=9365) groups based on the local government's targets for particulate matter reduction. We estimated the 10-year risk of incident CVD morbidity or mortality using a validated risk prediction model. We used a difference-in-difference model to assess the long-term association between CCAA implementation and predicted risk, with adjustments made for regional confounders and individual-level characteristics, including demographics, lifestyle factors, medical history, and indoor air pollution exposure. The relationship between changes in long-term exposure to PM2·5, PM10, and O3 and predicted risk after CCAA implementation was analysed using a linear model. The estimated risk differences associated with air pollutant changes were estimated based on the magnitude of changes and their corresponding effect sizes. FINDINGS: After the CCAA was implemented, PM2·5 and PM10 concentrations declined in both groups, but O3 concentrations increased. The intervention group showed a 3·95% (95% CI 3·18-4·72%) lower increase in predicted risk than the control group, with larger estimated differences under stricter enforcement. Between 2013 and 2021, each 10 μg/m3 change in PM2·5 concentration was positively associated with a 1·80 (1·34-2·27) percentage point change in predicted CVD risk, whereas each 10 μg/m3 change in PM10 concentration was associated with a 1·24 (0·84-1·63) percentage point change and each 10 μg/m3 change in O3 concentration with a 0·58 (0·33-0·83) percentage point change. Overall, the observed changes in air pollutants during the study period were associated with an average 6·6 percentage point reduction in predicted CVD risk. INTERPRETATION: The CCAA and improved air quality were associated with a slower increase in predicted CVD risk, supporting the necessity for stricter, multipollutant air quality policies to maximise public health benefits. FUNDING: National Natural Science Foundation of China, Kadoorie Charitable Foundation, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, Chinese Ministry of Science and Technology, and UK Wellcome Trust.

Journal Article↗

PubMed1976

Plasma 16 beta-hydroxydehydroepiandrosterone in normal and pathological conditions in man.

Plasma 16beta-hydroxydehydroepiandrosterone (16 beta-OH-DHEA) levels in normal subjects and patients with certain pathological conditions have been evaluated using radioimmunoassay of the steroid. Plasma 16 beta-OH-DHEA levels in normal subjects rose sharply during adolescence and then declined slowly throughout adult life: 192 +/- 54 (SE) pg/ml between 7 and 11 yrs., 395 +/- 22 pg/ml between 15 and 19 yrs, 330 +/- 29 pg/ml between 20 and 39 yrs., 291 +/- 35 pg/ml between 40 and 59 yrs., and 124 +/- 20 over 60 yrs. No significant difference was found between male and female subjects. Plasma 16 beta-OH-DHEA rose significantly (P less than 0.001) during ACTH stimulation, declined significantly (P less than 0.005) during dexamethasone suppression, declined significantly (P less than 0.05) during gonadal suppression, rose significantly (P less than 0.05) during gonadal stimulation and rose significantly (P less than 0.005) after the administration of WIN 24,540, an inhibitor of 3 beta-ol-dehydrogenase. The concentration of 16 beta-OH-DHEA in adrenal venous blood was higher than in inferior vena cava blood, but 16 beta-OH-DHEA in hepatic venous blood was not higher than 16 beta-OH-DHEA in arterial blood. It is inferred that 16 beta-OH-DHEA is secreted directly by the adrenal cortex and probably the gonads. Plasma 16 beta-OH-DHEA was elevated in normal pregnant women, pregnant women with toxemia, and in patients with Cushing's disease, ectopic ACTH-producing tumor, and congenital adrenal hyperplasia, but it was not elevated in patients with low-renin essential hypertension.

Adolescent↗