Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “population stratification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 631 records · Page 35Linked to original sources
PubMed1994

HLA class II and T-cell receptor beta chain polymorphisms in Belgian patients with rheumatoid arthritis: no evidence for disease association with the TCRBC2, TCRBV8 and TCRBV11 polymorphisms.

OBJECTIVES: To investigate whether T-cell receptor (TCR) beta chain germline alleles, either alone or in combination with a particular HLA-genotype, are associated with rheumatoid arthritis (RA). METHODS: Three restriction fragment length polymorphisms (RFLPs), detected with TCR constant (TCRBC2) and variable (TCRBV8, TCRBV11) gene segments were analysed in a representative group of Belgian, HLA class II-typed patients with RA, and in a group of Belgian control subjects. RESULTS: The study confirmed the known association of RA with the HLA-DRB1*0401/0404 genotype (RR = 2.14, 95% CI = 1.16-4.00) in the Belgian RA population. This association was even more pronounced in the patients with more severe RA (RR = 3.26, 95% CI = 1.55-6.89). These data suggest that the HLA-DRB1*04 genotype can be used as a marker for disease severity. Similar frequencies in patients and controls were observed for all TCRB RFLPs studied, and this was in spite of subgrouping the RA population according to criteria for disease stratification. CONCLUSION: While a clear association with HLA DRB1*0401/0404 is observed, no interactive effects were seen with RA, DR4, TCRBC2 and TCRBV alleles, implying that the combined presence of these polymorphic markers does not cause an increased susceptibility to RA, and does not predispose for more aggressive RA, nor for familial aggregation of the disease. These results argue against the hypothesis that TCRB polymorphisms play a crucial role in the susceptibility for RA.

Adult↗
PubMed1996

Benton Controlled Oral Word Association Test: reliability and updated norms.

The aim of this paper is to update the over 20-year-old normative data for the Benton Controlled Word Association (COWA) Test. In a sample of 360 normal volunteers, the age ranged between 16-70 years, and the educational level ranged from 7-22 years. Care was taken to ensure that the population was heterogeneous, yet the two stratifications of gender, four age, and three educational groups led to 24 cells with 15 individuals in each. Test-retest reliability was established by testing 30% of the sample after a 6-month delay, which represents a typical follow up duration between testings in a clinical setting. The two forms of the COWA revealed significant test-retest reliability. Generally, our updated values fall above the original normative values, which were derived from a less well-educated and rural sample. No major gender or age trends were noted, but the COWA test performances were influenced by education, i.e., as the level of education increased, the performance on the COWA increased. The only gender differences that were found were for the women in the highest educational group ( > 16 years), who performed significantly better that men in the highest educational group. An error analysis of repetitions or perseverations is provided, with cut-off scores according to age levels. Finally, the updated COWA norms are compared to the original norms as well as to other measures of word fluency.

Journal Article↗
PubMed2004

Transesophageal echocardiography-guided cardioversion of atrial fibrillation. Selection of a low-risk group for immediate cardioversion.

INTRODUCTION: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec. METHODS AND RESULTS: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01). CONCLUSION: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.

Aged↗
PubMed2006

Development and validation of a medication intensity scale derived from computerized pharmacy data that predicts emergency hospital utilization for persistent asthma.

OBJECTIVE: To validate a risk stratification scheme using computerized pharmacy data to predict emergency hospital utilization for persistent asthma. STUDY DESIGN: Retrospective cohort. METHODS: The development sample consisted of 1079 HMO members aged 18 to 56 years with persistent asthma. The scale used medication cut-points as predictors for next-year emergency hospital utilization in a stepwise logistic regression model. Prediction properties were evaluated in a validation sample of 24 370 patients aged 18 to 56 years in a separate persistent-asthma database. RESULTS: Increasing use of beta-agonists (odds ratio [OR] of 2.2 for 5-13 vs 0-4 canisters; OR of 2.4 for >13 vs 5-13 canisters) and oral corticosteroids (OR of 2.6 for >2 vs 0-2 dispensing events) in the first year independently predicted emergency hospital utilization in the second year. Assigning 1 point for exceeding each of the above 3 medication thresholds led to a 4-level medication intensity scale that was significantly (P <.0001) related to validated measures of asthma symptom severity, asthma control, and asthma quality of life in the development sample. In the validation sample, this scheme identified a high-risk group that was 6 times more likely than the low-risk group to require subsequent emergency hospital care, with overall sensitivity of 65% and specificity of 54%. This scale did not perform as well as a scale based on both baseline emergency hospital care and pharmacy data. CONCLUSION: This simple risk stratification scheme can be used for populations with persistent asthma for whom computerized pharmacy data, but not computerized prior utilization data, are available.

Adolescent↗
PubMed2006

Treatment decision-making for older patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: problems and approaches.

BACKGROUND AND OBJECTIVES: High-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are mainly diseases of patients over the age of 60 years. In these patients, intensive chemotherapy and/or allogeneic blood stem cell transplantation are the only curative treatment approaches, while non-curative options include low-dose chemotherapy or best supportive care alone. The basis for treatment decision-making in this clinically and biologically heterogeneous group is not well defined. DESIGN AND METHODS: In order to investigate treatment stratification patterns and outcomes in this population, we performed a systematic literature search in MedLine for relevant clinical reports published between 1989 and 2006. Only large population-based investigations and publications of clinical trials with more than 40 patients were analyzed. RESULTS: In 36 AML studies involving a total of 12,370 patients (median age 70 years) median overall survival approached 30 weeks for intensively treated patients. In patients receiving best supportive care alone, or best supportive care plus non-intensive treatment, median overall survival was 7.5 and 12 weeks, respectively. The complete remission rate after induction was 44%, and in those patients who achieved complete remission age no longer influenced prognosis. In 18 large studies approximately 50% of AML patients received induction therapy, 30% non-intensive chemotherapy and 20% supportive care only. INTERPRETATION AND CONCLUSIONS: Due to the scarcity of randomized AML/MDS trials in which older patients are assigned to either induction or less intense therapy, predictors to identify older patients most likely to benefit from intensive therapy and novel tools to optimize (or even standardize) recommendations are needed. We propose that in this patient population in the future, geriatric assessment instruments and comorbidity scoring are implemented in treatment decision-making.

Age Factors↗
PubMed1996

Genetic diversity of PTC taste sensitivity among tribal and caste populations of Andhra Pradesh, India.

The present paper reports the variability of PTC taste sensitivity among eight endogamous tribal populations inhabiting the Eastern Ghats of North Coastal Andhra Pradesh. It was compared with the genetic diversity of PTC taste sensitivity among tribal and caste populations of Andhra Pradesh. The tribal and caste groups present a relatively high genetic diversity, of which a major proportion is due to genetic differences within populations rather than that between populations. Castes show a higher heterogeneity than tribes, the difference being significant. The high genetic diversity found among Andhra populations may be attributed to social stratification and the practice of strict endogamy.

Ethnicity↗
PubMed1996

Use of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in the diagnosis of acromegaly and growth hormone deficiency in adults.

The goal of our study was to compare the clinical usefulness of plasma insulin-like growth factor-I (IGF-I) (with and without binding protein extraction) and IGF binding protein-3 (IGFBP-3) measurements in the diagnosis of growth hormone (GH) disorders in adults. IGF-I and IGFBP-3 concentrations were measured in 25 acromegalic and 25 GH-deficient adult (GHDA) subjects (20-76 years) by comparison to a control population (n = 81) after age and sex stratification. In untreated acromegaly, IGF-I and IGFBP-3 were clearly increased (10 times the mean of controls for unextracted IGF-I, 4 times for extracted IGF-I and 2 times for IGFBP-3). Using the mean + 2SD of the control population as the cut-off point, the sensitivity of IGF-I for the diagnosis of acromegaly was higher than that of IGFBP-3 (unextracted IGF-I: 96% and extracted IGF-I: 100% vs IGFBP-3: 76%). In GHDAs, IGF-I and IGFBP-3 were decreased (34% of the mean of controls for unextracted IGF-I, 37% for extracted IGF-I and 70% for IGFBP-3). Using the mean - 2SD of the control population as the cut-off point, the sensitivity of IGF-I measurement for the diagnosis of GHDA was relatively low, but better for unextracted (68%) than for extracted IGF-I (52%). The sensitivity of IGFBP-3 was much lower (36%), thus invalidating this parameter for the diagnosis of GHDA. Our observations demonstrate that IGF-I measurement is a more powerful tool than IGFBP-3 measurement for the diagnosis of GH disorders in adults. Both IGF-I and IGFBP-3 are very useful for the diagnosis of acromegaly, but they are less reliable for diagnosing GHDA, as normal IGF-I or IGFBP-3 values do not rule out GH deficiency.

Acromegaly↗
PubMedDate not supplied

[Clinical indications for implant of CID in patients with coronary heart disease and cardiac failure].

The mortality of the myocardial acute infarction has diminished with the introduction of the new strategies of reperfusion; this way, the number of patients with ventricular left dysfunction has increased. This one is a special population with risk greater than rest of people of suffering an event of cardiac sudden death (SD). This fact needs of a suitable process of stratification of the risk for SD that this population has and it is necessary measures of primary and secondary prevention to diminish the mortality of these patients. In this paper the clinical characteristics of this population by precedent of heart attack of the myocardium and/or ventricular left dysfunction are checked. These characters can suggest the indication for the implant of an automatic defibrillator.

Coronary Disease↗
PubMed2006

Relationship between self-reported odor intolerance and sensitivity to inhaled capsaicin: proposed definition of airway sensory hyperreactivity and estimation of its prevalence.

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between the behavioral consequences of self-reported odor sensitivity with the chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) and cough sensitivity to inhaled capsaicin. We also wanted to estimate the prevalence of airway sensory hyperreactivity (SHR), which was defined as a positive CSS-SHR score in combination with a positive capsaicin inhalation test result. DESIGN: A general population-based study with randomly selected individuals after stratification for age and gender. SETTING: Skövde Central Hospital, Departments of Lung Medicine and Otorhinolaryngology, Sweden. PARTICIPANTS: A total of 693 randomly selected individuals from a population-based study in which 595 persons (86%) responded to the CSS-SHR questionnaire. INTERVENTIONS: The individuals were divided into four groups with different odor sensitivity according to their CSS-SHR score. Of these, 137 individuals were randomly recruited for the capsaicin inhalation test. Capsaicin inhalation was performed with concentrations of 0.4 and 2.0 mumol/L in a randomized order. The number of coughs were registered and counted for 10 min from the start of each inhalation. MEASUREMENTS AND RESULTS: Of the 137 individuals who were recruited for the capsaicin inhalation test, 103 (75%) participated. Sixteen individuals had increased cough sensitivity and fulfilled the criteria for a positive capsaicin inhalation test result. Of the individuals with a positive capsaicin inhalation test result, > 80% also had a positive CSS-SHR score. Only 5% of the individuals with a negative CSS-SHR score had a positive capsaicin inhalation test result. The order of inhaled capsaicin concentration was found to influence the results. The prevalence of SHR with the definition given above was estimated to be 6.3% in this general population. CONCLUSIONS: A high CSS-SHR score was found to be directly related to the sensitivity for inhaled capsaicin, which made it possible to relate subjective data to objective findings.

Administration, Inhalation↗
PubMed2005

Changes in the light sensitivity of buried Polygonum aviculare seeds in relation to cold-induced dormancy loss: development of a predictive model.

The effect of cold (stratification) temperature on changes in the sensitivity of Polygonum aviculare seeds to light was investigated. Seeds buried in pots were stored under stratification temperatures (1.6, 7 and 12 degrees C) for 137 d. Seeds exhumed at regular intervals during storage were exposed to different light treatments. Germination responses obtained for seeds exposed to different light treatments and stratification temperatures were used to develop a model to predict the sensitivity of buried seeds to light. Seed sensitivity to light increased as dormancy loss progressed, showing the successive acquisition of low-fluence responses (LFR), very low-fluence responses (VLFR), and the loss of the light requirement for germination for a fraction of the seed population. These changes were inversely correlated to stratification temperature, allowing the use of a thermal time index to relate observed changes in seed light sensitivity to stratification temperature. The rate of increase in sensitivity of P. aviculare seeds to light during stratification is inversely correlated to soil temperature, and these changes in light sensitivity could be predicted in relation to temperature using thermal-time models.

Cold Temperature↗
PubMed2006

Microsatellite diversity and broad scale geographic structure in a model legume: building a set of nested core collection for studying naturally occurring variation in Medicago truncatula.

BACKGROUND: Exploiting genetic diversity requires previous knowledge of the extent and structure of the variation occurring in a species. Such knowledge can in turn be used to build a core-collection, i.e. a subset of accessions that aim at representing the genetic diversity of this species with a minimum of repetitiveness. We investigate the patterns of genetic diversity and population structure in a collection of 346 inbred lines representing the breadth of naturally occurring diversity in the Legume plant model Medicago truncatula using 13 microsatellite loci distributed throughout the genome. RESULTS: We confirm the uniqueness of all these genotypes and reveal a large amount of genetic diversity and allelic variation within this autogamous species. Spatial genetic correlation was found only for individuals originating from the same population and between neighbouring populations. Using a model-based clustering algorithm, we identified four main genetic clusters in the set of individuals analyzed. This stratification matches broad geographic regions. We also identified a set of "admixed" individuals that do not fit with this population structure scheme. CONCLUSION: The stratification inferred is discussed considering potential historical events like expansion, refuge history and admixture between neighbouring groups. Information on the allelic richness and the inferred population structure are used to build a nested core-collection. The set of inbred lines and the core collections are publicly available and will help coordinating efforts for the study of naturally occurring variation in the growing Medicago truncatula community.

DNA, Plant↗
PubMed1999

[Epidemiological stratification of malaria in the Comoro archipelago].

In the Comoros Islands, the level of malarial endemicity varies greatly from one island to the other, even though the total area (4 islands) covers less than 2,300 km2 and has a population of some 600,000 people only. The epidemiological stratification is based on the diversity of human and physical characterisation. They both determine the presence and the behaviour as well as the size of the vector's populations. Vectorial dynamics can explain varying levels of endemicity given parasitological indicators and specific morbidity. Analyzing these criteria shows up different epidemiological features and serves as a basic guideline for malaria control. The efficiency of this control depends on the relationships between the intensity and the length of the transmission, in the framework of protection mechanisms; it is of crucial importance for clinical treatment. Further elements are the age of the patient, the season and the geographic situation of the area. Stratification provides explanations for these relationships and helps to define antimalarial programmes adapting to each situation a range of therapeutic and antivectorial methods. The availability and accessibility of anti-malarial medicine is the minimum requirement for reducing mortality: domestic spray insecticides for reducing transmission are effective for several years and should be followed by the use of mosquito nets or curtains impregnated with pyrethrinoids, and in the particular case of Grande Comore, the use of larvivorous fish. As anywhere else, the economic development, which is dependent on political stability, is the essential basis for malaria control.

Age Factors↗
PubMed2002

Relative and absolute HLA-DQA1-DQB1 linked risk for developing type I diabetes before 40 years of age in the Belgian population: implications for future prevention studies.

HLA-DQ genotyping remains the cornerstone of genetic risk stratification in type I diabetes prediction and prevention studies. We developed a genetic screening strategy for predisposition to type I diabetes in the Belgian population based upon HLA-DQA1-DQB1 typing and taking into account the age at clinical onset. A group of 1866 autoantibody-positive type I patients below age 40 years recruited by the Belgian Diabetes Registry and a group of 750 control subjects were DQA1-DQB1 genotyped. In the total study population 16 different DQA1-DQB1 haplotypes were revealed, allowing the stratification of 81 genotypes in ten different genotype groups. Apart from the highest risk DQA1*-DQB1* genotype 0301-0302/0501-0201 (odds ratio 21; absolute risk 6%), three other genotype groups conferred a highly significant disease risk (p < 10(-6)). Altogether, these susceptibility genotypes were carried by 9% of the control subjects versus 60% of the patients diagnosed before age 40 years and up to 70% of those under age 5 years. All other genotypes were protective, neutral, infrequent or associated with a moderate protection or susceptibility. A strong, although not absolute protection was conferred by DQB1*0602-positive haplotypes (odds ratio = 0.03). This study in a large cohort of autoantibody-positive patients shows that a DQA1-DQB1-based genotyping strategy allows the identification of a subgroup representing less than 10% of the Belgian population but harbouring the majority of future type I patients arising in childhood or early adulthood. Future prediction and prevention studies should take into account the age dependency of this HLA-DQ associated risk.

Adolescent↗
PubMed2005

A direct approach to control short term population dynamics in time series studies.

BACKGROUND: Short term population dynamics is an important issue in several epidemiological studies. Usually, calendar time or dummy variables are used to control indirectly for this confounding. This study tested a direct method. METHODS: The study compared as proxy variables of population dynamics the summer 2003 data of cooking gas consumptions, solid urban waste production, and television access for the municipality of Bologna (Italy). RESULTS: Solid urban waste production and television access data showed similar trends. Considerably different were the >65 year olds estimates with respect to total population based on television access. CONCLUSIONS: Television access data are probably the best indicator in the estimates of population dynamics in large or densely populated areas, especially because of the possibility of stratifications with respect to age.

Aged↗
PubMed2025

Breast Cancer Risk Stratification in Black Women: Current Status and Potential Solutions to Improve Accuracy.

Breast cancer risk stratification models identify individuals at increased risk, allowing earlier screening than for those at average risk and potentially improving health outcomes. Due to the increasing rates of breast cancer in individuals aged <40 years, especially among Black females, the American College of Radiology now recommends all females initiate breast cancer risk assessment by age 25 years. Several breast cancer risk prediction models are readily available, including the Gail Model, Breast Cancer Surveillance Consortium Risk Calculator, BOADICEA, and Tyrer-Cuzick Model. However, because these models were primarily developed using data from White women of European ancestry, they may underestimate risk in Black women. Indeed, current evidence suggests that these models underpredict breast cancer risk among Black women, particularly those of African ancestry. Although cancer risk prediction models typically incorporate personal characteristics, family history of cancer, and hormonal and lifestyle factors, inherited breast cancer genes can also increase risk for breast cancer. Beyond monogenic inherited breast cancer genes that increase breast cancer risk, emerging data suggest that single nucleotide polymorphisms identified through genome-wide association studies (GWAS) may be used to generate polygenic risk scores, which may further refine breast cancer risk. However, GWAS data are also primarily gathered from European ancestry females, further reducing the ability to accurately stratify breast cancer risk in non-European ancestry populations. Current data highlight the importance of ensuring representation from all populations in developing cancer risk prediction models, conducting genomics research, and designing effective implementation strategies to enhance the use of these models in routine clinical care. Although new analytic methods and models are being developed to improve breast cancer risk stratification across populations, it remains critical to assess the utility and calibration of existing and new models to ensure applicability across non-European ancestry populations.

Humans↗
PubMed2026

Unique Features of Melanoma Risk and Diagnosis in Red-Haired Populations.

Cutaneous melanoma is the most lethal skin cancer, and risk is strongly shaped by pigmentary phenotype. The red-hair color phenotype, marked by red hair, fair skin, freckling, and poor tanning, carries elevated melanoma risk driven largely by loss-of-function variants in the melanocortin 1 receptor gene (MC1R). This risk is not explained by reduced ultraviolet protection alone. Impaired MC1R signaling shifts melanogenesis from photoprotective eumelanin toward pheomelanin, a pigment associated with oxidative stress and partly ultraviolet-independent melanomagenesis. MC1R may also influence melanoma susceptibility through pigment-independent effects on DNA damage responses, repair signaling, and genomic stability. These mechanisms support investigation of MC1R genotype, visible phenotype, nevus burden, pigment chemistry, and imaging-derived lesion metrics as complementary tools for risk stratification. Diagnosis is also distinctive in this population. Amelanotic and hypomelanotic melanomas are associated with the red-hair color phenotype, and their low pigmentary contrast may delay recognition and contribute to diagnosis at a more advanced stage. This review integrates genetic, molecular, biomarker, diagnostic, and therapeutic literature specific to red-haired populations. We argue that elevated biological susceptibility and diagnostic difficulty compound one another, and we outline priorities for MC1R-informed surveillance, imaging adapted to pigment-poor disease, pharmacologic modulation of MC1R-related pathways, and prospective risk models integrating genotype, phenotype, nevus burden, pigment biology, and imaging.

Humans↗
PubMed2004

Effects of hydrographic barriers on population genetic structure of the sea star Coscinasterias muricata (Echinodermata, Asteroidea) in the New Zealand fiords.

New Zealand's 14 deep-water fiords possess persistent salinity stratification and mean estuarine circulation that may serve to isolate populations of marine organisms that have a dispersal larval phase. In order to investigate this idea, we analysed the population structure of the sea star Coscinasterias muricata using a mitochondrial DNA marker. Genetic differentiation among populations of C. muricata was analysed using 366 base pairs of mtDNA D-loop. We compared populations from the fiords with several others sampled from around New Zealand. At a macro-geographical scale (> 1000 km), restricted gene flow between the North and South Islands was observed. At a meso-geographical scale (10-200 km), significant population structure was found among fiords and between fiords and open coast. The pattern of population genetic structure among the fiords suggests a secondary contact between a northern population and a southern one, separated by a contact or mixing zone. These populations may have diverged by the effects of random genetic drift and population isolation as a consequence of the influence of estuarine circulation on dispersal. In northern Fiordland, genetic structure approximated an isolation by distance model. However, the pattern in genetic differences suggests that distance alone cannot explain the most divergent populations and that fiord hydrography may increase the effect of genetic drift within populations in the fiords. Finally, our study indicates that populations within the fiords underwent recent rapid expansion, followed most probably by genetic drift due to a lack of gene flow among the fiords.

Animals↗
PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗