European Populations Research Articles

Mendelian randomization study of childhood asthma and chronic obstructive pulmonary disease in European and East Asian population

ObjectiveThe present study aimed to explore the potential causal relationship between childhood asthma and chronic obstructive pulmonary disease (COPD) in European and East Asian populations with Mendelian randomization (MR) analysis. MethodsBased on summary data from genome-wide association studies, single nucleotide polymorphisms (SNPs) associated with childhood asthma were used as instrumental variables. The MR analysis employed the inverse variance weighting, MR-Egger regression and weighted median method to estimate the causal effect between childhood asthma and COPD in European and East Asian populations. Cochran's Q test, MR-PRESSO method and MR-Egger intercept were used to detect heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis applied to assess the effect of removing individual SNP on the estimate of causal association. ResultsThe MR analysis showed no genetic causal relationship between childhood asthma and COPD. The results of Cochran's Q test, MR-PRESSO and MR-Egger regression indicated the absence of heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis showed no significant difference in the statistical results after exclusion of single SNPs. ConclusionsThe MR analysis revealed that there is no causal relationship between childhood asthma and COPD at the genetic level in both European and East Asian populations. Additionally, due to the presence of shared confounding factors and pathogenic genes, further research is needed to comprehensively assess the relationship between childhood asthma and COPD.

Ectoparasites of the European wildcat (Felis silvestris) in Germany

Understanding the impact of parasites on wildlife populations is an important aspect of conservation management. However, research on ectoparasites in wildlife can be difficult, as examinations of live animals which are not habituated to human handling are often impossible. The European wildcat (Felis silvestris) is a strictly protected wildlife species whose population has been recovering in Germany in recent decades. Several studies from different European countries have investigated the parasitological status of European wildcat populations. However, most of these studies assessed endoparasite infections, whereas ectoparasite infestations have often been neglected. To fill this knowledge gap for wildcats in Germany, 131 dead found specimens were examined for ectoparasites by macroscopic and microscopic examination of the fur and the ear canals. Infestation with ectoparasites was present in 84.0% (110/131) of the wildcats. Ticks showed the highest prevalence with 72.5% (95/131) of wildcats infested, with 49.6% (65/131) infested with Ixodes ricinus and 36.6% (48/131) with Ixodes hexagonus/canisuga. A total of 27.5% (36/131) of the wildcats were positive for at least one flea species. Of the nine different flea species identified by morphology and/or molecular analyses, Ceratophyllidae were most common (16.8% [22/131]), with Ceratophyllus sciurorum confirmed on 12.2% (16/131) and Nosopsyllus fasciatus on 1.5% (2/131) animals, followed by Pulex irritans (5.3% [7/131]), Spilopsyllus cuniculi (3.8% [5/131]), Chaetopsylla spp. (3.1% [4/131]) (2/131 Chaetopsylla trichosa and 1/131 Chaetopsylla globiceps), Ctenocephalides felis (1.5% [2/131]), Archaeopsylla erinacei (1.5% [2/131]) and Ctenophthalmus baeticus (0.8% [1/131]). Further, 23.7% (31/131) of the wildcats harboured mites, identified as Trombicula autumnalis in 12.2% (16/131) and Otodectes cynotis in 4.8% (6/124) of cases. The only louse species detected was Felicola hercynianus with a prevalence of 2.3% (3/131). Infestation intensities ranged from 1 to 86 ticks, 1–49 fleas, 1–1896 mites, and 1–92 F. hercynianus per wildcat. This study demonstrates that a variety of ectoparasites infests wildcats in Germany, but they do not seem to have a serious impact on the general health of wildcats, as judged by the hosts' mostly good or very good nutritional condition. In addition, the potential risk to domestic cats (Felis catus) and humans posed by the wildcats’ ectoparasites, appears to be low but present.

Frailty index is an independent predictor of all-cause and cardiovascular mortality in Eastern Europe: a multicentre cohort study

BackgroundThis study investigates the association between frailty and mortality in Eastern European populations, which remains largely unexplored compared with Western Europe. The aim is to assess the risk of all-cause...

Causal associations of osteoporosis with stroke: a bidirectional Mendelian randomization study.

The correlation between OP and stroke is unclear. This study used a two-sample bidirectional MR study to determine the causal relationship between OP and stroke. Summary data from genome-wide association studies (GWAS) were used to perform MR analyses. Summary data for OP (n = 300,147), OP with pathological fracture (n = 239,702), and postmenopausal OP with pathological fracture (n = 182,601) were extracted from large-scale GWAS and meta-analyses of European populations in the FinnGen consortium. Similarly, summary data for stroke (n = 446,696), ischemic stroke (IS, n = 440,328), small vessel stroke (SVS, n = 198,048), large artery atherosclerosis stroke (LAS, n = 150,765), and cardioembolic stroke (CES, n = 211,763) were extracted from the MEGASTROKE consortium. Methods such as inverse variance weighted, MR-Egger, and weighted median were applied to perform various outcome analyses for MR. The results demonstrated significant positive causality of stroke, IS, and LAS on OP (stroke: odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.04-1.85, and P = 0.027; IS, OR: 2.02, 95% CI: 1.05-3.87, and P = 0.035; LAS: OR: 1.29, 95% CI: 1.08-1.55, and P = 0.005), positive causality of LAS on OP with pathological fracture (LAS: OR: 1.69, 95% CI: 1.18-2.42, and P = 0.004), and positive causality of stroke and LAS on postmenopausal OP with pathological fracture (stroke: OR: 2.02, 95% CI: 1.05-3.87, and P = 0.035; LAS, OR: 1.75, 95% CI: 1.06-2.90, and P = 0.030). There was also a significant positive causal relationship between OP and SVS (OP, OR: 1.08, 95% CI: 1.01-1.14, and P = 0.021). In conclusion, there is a causal relationship between stroke and OP, suggesting that they may be potential risk factors for each other. Therefore, patients with stroke should receive timely prevention for OP, OP with pathological fracture, and postmenopausal OP with pathological fracture. Similarly, patients with OP may need to be evaluated for potential cardiovascular risks.

Meta-analysis of genome-wide association studies of stable warfarin dose in patients of African ancestry

AbstractWarfarin dose requirements are highly variable because of clinical and genetic factors. Although genetic variants influencing warfarin dose have been identified in European and East Asian populations, more work is needed to identify African-specific genetic variants to help optimize warfarin dosing. We performed genome-wide association studies (GWASs) in 4 African cohorts from Uganda, South Africa, and Zimbabwe, totaling 989 warfarin-treated participants who reached stable dose and had international normalized ratios within therapeutic ranges. We also included 2 African American cohorts recruited by the International Warfarin Pharmacogenetics Consortium (n = 316) and the University of Alabama at Birmingham (n = 199). After the GWAS, we performed standard error-weighted meta-analyses and then conducted stepwise conditional analyses to account for known loci in chromosomes 10 and 16. The genome-wide significance threshold was set at P < 5 × 10−8. The meta-analysis, comprising 1504 participants, identified 242 significant SNPs across 3 genomic loci, with 99.6% of these located within known loci on chromosomes 10 (top SNP: rs58800757, P = 4.27 × 10−13) and 16 (top SNP: rs9925964, P = 9.97 × 10−16). Adjustment for the VKORC1 SNP -1639G>A revealed an additional locus on chromosome 2 (top SNPs rs116057875/rs115254730/rs115240773, P = 3.64 × 10−8), implicating the MALL gene, that could indirectly influence warfarin response through interactions with caveolin-1. In conclusion, we reaffirmed the importance of CYP2C9 and VKORC1 in influencing warfarin dose requirements, and identified a new locus (MALL), that still requires direct evidence of biological plausibility.

Inference of host-pathogen interaction matrices from genome-wide polymorphism data.

Host-pathogen coevolution is defined as the reciprocal evolutionary changes in both species due to genotype x genotype (GxG) interactions at the genetic level determining the outcome and severity of infection. While co-analyses of host and pathogen genomes (co-GWAs) allow us to pinpoint the interacting genes, these do not reveal which host genotype(s) is/are resistant to which pathogen genotype(s). The knowledge of this so-called infection matrix is important for agriculture and medicine. Building on established theories of host-pathogen interactions, we here derive four novel indices capturing the characteristics of the infection matrix. These indices can be computed from full genome polymorphism data of randomly sampled uninfected hosts, as well as infected hosts and their pathogen strains. We use these indices in an Approximate Bayesian Computation method to pinpoint loci with relevant GxG interactions and to infer their underlying interaction matrix. In a combined SNP data set of 451 European humans and their infecting Hepatitis C Virus (HCV) strains and 503 uninfected individuals, we reveal a new human candidate gene for resistance to HCV and new virus mutations matching human genes. For two groups of significant human-HCV (GxG) associations, we infer a gene-for-gene infection matrix, which is commonly assumed to be typical of plant-pathogen interactions. Our model-based inference framework bridges theoretical models of GxG interactions with host and pathogen genomic data. It, therefore, paves the way for understanding the evolution of key GxG interactions underpinning HCV adaptation to the European human population after a recent expansion.

Excellence in the management of Advanced Hybrid Closed-Loop Systems: Lessons from the Polish cohort

BackgroundThe aim of the study was to analyze the real-world performance of MiniMed 780G (MM780G) Advanced Hybrid Closed Loop (AHCL) system users from Poland (PL) and compare it to the European region excluding Poland (EU-PL) in order to identify factors contributing to potential differences. The former achieved some of the best Time in Range (TIR) results globally using this technology. MethodsCareLink Personal data uploaded by MM780G system users from August 2020 to December 2022 were analyzed. ResultsThe Polish users (N=1304) on average reached to TIR of 79.1 ± 8.7 % (vs 73.0 ± 10.0 % for EU-PL, N=55659), a TBR<54 mg/dL of 0.6 ± 0.7 % (vs 0.4 ± 0.6 %) and a TBR<70 mg/dL of 2.9 ± 2.1 % (vs 2.1 ± 1.8 %). The adoption rate of optimal settings (i.e, GT=100 mg/dL, AIT=2hr) in PL was high (19.7 % vs 6.3 %), and filtering on optimal setting users led to less pronounced differences in glycemic control between PL and EU-PL. A univariable analysis with post-AHCL TIR showed that geography itself (PL vs EU-PL) is not a significant contributor to a high post-AHCL TIR (p = 0.15), and that much of the Polish post-AHCL TIR can be explained by the high pre-AHCL TIR. ConclusionThe Polish MM780G users achieved better glycemic control than the general European population (excluding Poland). This is largely attributable to the adoption of optimal settings in Poland and the already high glycemic outcomes at system start. As these characteristics can be implemented elsewhere, we believe this outstanding result can be obtained in other countries as well.

Revision of the Festuca marginata “group” (Festuca sect. Festuca, Poaceae) in Southern Europe, with special reference to France, Italy and Greece

ABSTRACT The Festuca marginata group includes several taxa of glaucous, thick-leaved fescues with three sclerenchyma strands, first described by Hackel as Festuca ovina subsp. laevis, which are common in the Euro-Mediterranean area. Ten different taxa (species and subspecies) are currently recognized in this group. Nevertheless, taxonomical works typically have only a local (mostly national) scope, and the recognized taxa show only few or negligible morphological differences, making their separate taxonomic status doubtful. Here we provide morphological, karyological, and genetic analysis (ISSR, flow cytometry) of the Festuca marginata group based on populations in a larger geographical scale including Central and Southern-Eastern Europe. We found that most of the local taxa are difficult to definitively distinguish and we suggest the whole group be treated as a single species, Festuca marginata, with two subspecies reflecting major differences in morphology and genome size between the Greece subsp. heldreichii and the remaining European populations, referred to as subsp. marginata.

Assessment of the causal relationship between inflammatory bowel diseases and chronic kidney diseases: A two-sample bidirectional mendelian randomization study among European population.

Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear. We determined the causal association between IBD and CKD by performing two-sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open-access genome-wide association studies (GWAS) among European ancestry. IVs-outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse-variance-weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta-analysed. Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016-1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027-1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969-1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965-1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948-1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963-1.089, p = 0.447). We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD.

Food Supplements and Their Use in Elderly Subjects-Challenges and Risks in Selected Health Issues: A Narrative Review.

The European population is ageing. Food Supplements (FSs) are foods with particular characteristics, consumed by elderly people for various purposes, including combating nutritional deficits. Their consumption in this age group, associated with a high prevalence of polypharmacy, can enhance interactions. Potential drug-food (or food supplements), drug-drug interactions and polypharmacy are common health issues among older adults. The prevalence of polypharmacy is high, and preliminary data also indicate that there is significant FS use, increasing the risk of the duplication of therapies and various adverse reactions as well as drug-FS and FS-FS interactions. Therefore, the intervention of health professionals in mitigating these risks is essential. This review highlights and discusses the association between FSs, polypharmacy, and adverse reactions due to the risk of potential interactions between these products. Moreover, it also provides current scientific evidence regarding the use of FSs by the elderly. A review of the challenges, advantages, and risks of using FSs in elderly people who are malnourished and/or polymedicated, focusing on the good practises needed to support healthy ageing, is presented. In this regard, this paper aims to help health professionals better deal with the issue of the use of multiple FSs and polypharmacy, overcome the malnutrition problem, and improve the health and well-being of older adults.

Local Ancestry Inference Based on Population-Specific Single-Nucleotide Polymorphisms-A Study of Admixed Populations in the 1000 Genomes Project.

Human populations have interacted throughout history, and a considerable portion of modern human populations show evidence of admixture. Local ancestry inference (LAI) is focused on detecting the genetic ancestry of chromosomal segments in admixed individuals and has wide applications. In this work, we proposed a new LAI method based on population-specific single-nucleotide polymorphisms (SNPs) and applied it in the analysis of admixed populations in the 1000 Genomes Project (1KGP). Based on population-specific SNPs in a sliding window, we computed local ancestry information vectors, which are moment estimators of local ancestral proportions, for two haplotypes of an admixed individual and inferred the local ancestral origins. Then we used African (AFR), East Asian (EAS), European (EUR) and South Asian (SAS) populations from the 1KGP and indigenous American (AMR) populations from the Human Genome Diversity Project (HGDP) as reference populations and conducted the proposed LAI analysis on African American populations and American populations in the 1KGP. The results were compared with those obtained by RFMix, G-Nomix and FLARE. We demonstrated that the existence of alleles in a chromosomal region that are specific to a particular reference population and the absence of alleles specific to the other reference populations provide reasonable evidence for determining the ancestral origin of the region. Contemporary AFR, AMR and EUR populations approximate ancestral populations of the admixed populations well, and the results from RFMix, G-Nomix and FLARE largely agree with those from the Ancestral Spectrum Analyzer (ASA), in which the proposed method was implemented. When admixtures are ancient and contemporary reference populations do not satisfactorily approximate ancestral populations, the performances of RFMix, G-Nomix and FLARE deteriorate with increased error rates and fragmented chromosomal segments. In contrast, our method provides fair results.

Anti-Immigration Agenda in the Rhetoric of European Right-Wing Populism: The Case of the “True Finns” Party

Anti-Immigration Agenda in the Rhetoric of European Right-Wing Populism: The Case of the “True Finns” Party

Application of EFSA EU menu database and R computing language to calculate the green chlorophyll intake in the European population

The growing evidence of the health benefits of chlorophyll pigments and the claims that could arise from industry and academia require data on their common dietary intakes. This study presents data on the chronic intake of green chlorophyll in 23 European countries using standardised methodologies to manage food consumption data within the EU Menu methodology. A mean intake of 207.12 mg of green chlorophylls/(d × person) for the adult population was calculated, considering significant covariates. The hierarchical cluster and partial least squares discriminant analysis (PLS-DA) techniques were applied to analyse intake disparities by region and age groups, identifying common food sources of green chlorophylls, such as olive oil, kale, and spinach. This paper presents a modern mathematical approach for obtaining novel information from existing databases of food composition data. Future challenges include building a comprehensive chlorophyll composition database for foods and extending the estimation to non-green chlorophyll pigments and metallo-chlorophyll food colourants.

Mendelian Randomization and Bayesian Colocalization Analysis Implicate Glycoprotein VI as a Potential Drug Target for Cardioembolic Stroke in South Asian Populations.

Circulating plasma proteins are clinically useful biomarkers for stroke risk. We examined the causal links between plasma proteins and stroke risk in individuals of South Asian ancestry. We applied proteome-wide Mendelian randomization and colocalization approaches to understand causality of 2922 plasma proteins on stroke risk in individuals of South Asian ancestry. We obtained genetic instruments (proxies) for plasma proteins from the UK Biobank (N=920). Genome-wide association studies summary data for strokes (N≤11 312) were sourced from GIGASTROKE consortium. Our primary approach involved the Wald ratio or inverse-variance-weighted methods, with statistical significance set at false discovery rate <0.1. Additionally, a Bayesian colocalization approach assessed shared causal variants among proteome, transcriptome, and stroke phenotypes to minimize bias from linkage disequilibrium. We found evidence of a potential causal effect of plasma GP6 (glycoprotein VI) levels on cardioembolic stroke (odds ratio [OR]Wald ratio=2.53 [95% CI, 1.59-4.03]; P=9.2×10-5, false discovery rate=0.059). Generalized Mendelian randomization accounting for correlated single nucleotide polymorphisms (SNPs), with the P value threshold at P<5×10-8 and clumped at r2=0.3, showed consistent direction of effect of GP6 on cardioembolic stroke (ORgeneralized inverse-variance-weighted=2.21 [95% CI, 1.46-3.33]; P=1.6×10-4). Colocalization analysis indicated that plasma GP6 levels colocalize with cardioembolic stroke (posterior probability=91.4%). Multitrait colocalization combining transcriptome, proteome, and cardioembolic stroke showed moderate to strong evidence that these 2 traits colocalize with GP6 expression in the coronary artery and brain tissues (multitrait posterior probability>50%). The potential causal effect of GP6 on cardioembolic stroke was not significant in European populations (ORinverse-variance-weighted=1.08 [95% CI, 0.93-1.26]; P=0.29). Our joint Mendelian randomization and colocalization analyses suggest that genetically predicted GP6 is potentially causally associated with cardioembolic stroke risk in individuals of South Asian ancestry. As genetic data on individuals of South Asian ancestry increase, future Mendelian randomization studies with larger sample size for plasma GP6 levels should be implemented to further validate our findings. Additionally, clinical studies will be necessary to verify GP6 as a therapeutic target for cardioembolic stroke in South Asians.

Haplotype analysis identifies functional elements in monoclonal gammopathy of unknown significance

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10−8) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.

Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries

Meat consumption could increase the risk of type 2 diabetes. However, evidence is largely based on studies of European and North American populations, with heterogeneous analysis strategies and a greater focus on red meat than on poultry. We aimed to investigate the associations of unprocessed red meat, processed meat, and poultry consumption with type 2 diabetes using data from worldwide cohorts and harmonised analytical approaches. This individual-participant federated meta-analysis involved data from 31 cohorts participating in the InterConnect project. Cohorts were from the region of the Americas (n=12) and the Eastern Mediterranean (n=2), European (n=9), South-East Asia (n=1), and Western Pacific (n=7) regions. Access to individual-participant data was provided by each cohort; participants were eligible for inclusion if they were aged 18 years or older and had available data on dietary consumption and incident type 2 diabetes and were excluded if they had a diagnosis of any type of diabetes at baseline or missing data. Cohort-specific hazard ratios (HRs) and 95% CIs were estimated for each meat type, adjusted for potential confounders (including BMI), and pooled using a random-effects meta-analysis, with meta-regression to investigate potential sources of heterogeneity. Among 1 966 444 adults eligible for participation, 107 271 incident cases of type 2 diabetes were identified during a median follow-up of 10 (IQR 7-15) years. Median meat consumption across cohorts was 0-110 g/day for unprocessed red meat, 0-49 g/day for processed meat, and 0-72 g/day for poultry. Greater consumption of each of the three types of meat was associated with increased incidence of type 2 diabetes, with HRs of 1·10 (95% CI 1·06-1·15) per 100 g/day of unprocessed red meat (I2=61%), 1·15 (1·11-1·20) per 50 g/day of processed meat (I2=59%), and 1·08 (1·02-1·14) per 100 g/day of poultry (I2=68%). Positive associations between meat consumption and type 2 diabetes were observed in North America and in the European and Western Pacific regions; the CIs were wide in other regions. We found no evidence that the heterogeneity was explained by age, sex, or BMI. The findings for poultry consumption were weaker under alternative modelling assumptions. Replacing processed meat with unprocessed red meat or poultry was associated with a lower incidence of type 2 diabetes. The consumption of meat, particularly processed meat and unprocessed red meat, is a risk factor for developing type 2 diabetes across populations. These findings highlight the importance of reducing meat consumption for public health and should inform dietary guidelines. The EU, the Medical Research Council, and the National Institute of Health Research Cambridge Biomedical Research Centre.

Heat vulnerability: health impacts of heat on older people in urban and rural areas in Europe.

Exposure to extreme heat is associated with both increased morbidity and mortality, especially in older people. Health burdens associated with heat include heat stroke, diabetes mellitus, hypertension, ischemic heart diseases, heart failure and arrhythmia, pulmonary diseases but also injuries, problems with activities of daily living, and mental disorders. In Europe, there are remarkable spatial differences in heat exposure between urban and less populated areas. In Austria, for example, there is asignificant gradual association between population density and the number of heat days, where the gradient of urbanization also follows the gradient of sea level. The European population is continuously ageing, especially in rural areas. Older adults are especially vulnerable to negative health consequences resulting from heat exposure, due to a lack of physiological, social, cognitive, and behavioral resources. Older people living in urban areas are particularly at risk, due to the urban heat island effect, the heat-promoting interplay between conditions typically found in cities, such as alack of vegetation combined with ahigh proportion of built-up areas; however, older people living in rural regions often have less infrastructure to cope with extreme heat, such as fewer cooling centers and emergency services. Additionally, older adults still engaged in agricultural or forestry activities may be exposed to high temperatures without adequate protection or hydration. More research is required to examine factors responsible for heat vulnerability in older adults and the interactions and possibilities for increasing resilience in older urban and rural populations to the health consequences of heat.

Genome-wide SNP assessment of contemporary European red deer genetic structure highlights the distinction of peripheral populations and the main admixture zones in Europe.

Genome-wide technologies open up new possibilities to clarify questions on genetic structure and phylogeographic history of taxa previously studied with microsatellite loci and mitochondrial sequences. Here, we used 736 individual red deer (Cervus elaphus) samples genotyped at 35,701 single nucleotide polymorphism loci (SNPs) to assess the population structure of the species throughout Europe. The results identified 28 populations, with higher degrees of genetic distinction in peripheral compared to mainland populations. Iberian red deer show high genetic differentiation, with lineages in Western and Central Iberia maintaining their distinctiveness, which supports separate refugial ranges within Iberia along with little recent connection between Iberian and the remaining Western European populations. The Norwegian population exhibited the lowest variability and the largest allele frequency differences from mainland European populations, compatible with a history of bottlenecks and drift during post-glacial colonization from southern refugia. Scottish populations showed high genetic distance from the mainland but high levels of diversity. Hybrid zones were found between Eastern and Western European lineages in Central Europe as well as in the Pyrenees, where red deer from France are in close contact with Iberian red deer. Anthropogenic restocking has promoted the Pyrenean contact zone, admixture events in populations on the Isle of Rum and in the Netherlands, and at least partly the admixture of the two main lineages in central-eastern Europe. Our analysis enabled detailed resolution of population structure of a large mammal widely distributed throughout Europe and contributes to resolving the evolutionary history, which can also inform conservation and management policies.

Exploring the genetic causal relationship between physical activity and migraine in European population based on Mendelian randomization analysis.

Previous studies have shown a connection between physical activity and migraines, but they don't prove a cause-and-effect relationship due to potential biases in observational methods. Utilizing accelerometer-measured physical activity data from a cohort of 377,234 participants in the UK Biobank and information from 599,356 European migraine patients (including 48,975 cases and 550,381 controls) obtained from 24 cohorts, we performed a bidirectional Mendelian randomization analysis to investigate the genetic bidirectional causal relationship between accelerometer-measured physical activity and migraines. Research findings indicated a slight negative genetic correlation between "average acceleration" physical activity (rg = -0.091, p = 0.011), overall physical activity (rg = -0.081, p = 0.017), and migraine. Nevertheless, no shared genetic components were observed between migraine and "fraction of accelerations > 425 mg" of physical activity (rg = -0.124, p = 0.076). The study results also demonstrated a lack of genetic bidirectional causality between accelerometer-measured physical activity and migraine ("average acceleration", OR = 1.002, 95% CI 0.975-1.031, p = 0.855, "fraction of accelerations > 425 mg", OR = 1.127, 95% CI 0.802-1.583, p = 0.488, overall physical activity, OR = 0.961, 95% CI 0.713-1.296, p = 0.799), and vice versa. Additionally, this lack of causal association persists even after adjusting for obesity (OR = 1.005, p = 0.578), education (OR = 1.019, p = 0.143), and depression (OR = 1.005, p = 0.847), either separately or simultaneously. The Mendelian randomization results based on genetic data do not provide support for a causal association between physical activity and migraine.

SGLT-2 inhibitors are beneficial in reducing the risk of thyroid cancer: findings from a Mendelian randomization study.

Previous studies have investigated the association between diabetes medications and thyroid cancer, but the results have not been conclusive. This study used a Mendelian randomization approach to investigate the causal relationship between diabetes medications and thyroid cancer (TC). Exposures were six major diabetes medications target, while outcomes were TC and its differentiated forms, including papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Mendelian randomization was conducted using IVW, MR-Egger, and weighted median methods. Tests for heterogeneity, horizontal pleiotropy, and leave-one-out were also performed. In European populations, SGLT2 inhibitors were significantly negatively associated with TC (OR 0.051, 95% CI 0.006-0.465, P = 0.0082) as well as PTC (OR 0.034, 95% CI 0.003-0.411, P = 0.0079), while no correlation was found with FTC. These findings remained consistent even after applying the Bonferroni correction. The evidence suggests that SGLT2 inhibitors could be potential therapeutic targets for TC, especially for PTC, in European populations. However, further large-scale randomized controlled trials are necessary to verify their ability to reduce the risk of and treat these types of cancer.