European Journal of Epidemiology最新文献

{"title":"Evidence triangulation in health research","authors":"Sirena Gutierrez, M. Maria Glymour, George Davey Smith","doi":"10.1007/s10654-024-01194-6","DOIUrl":"https://doi.org/10.1007/s10654-024-01194-6","url":null,"abstract":"<p>For many important questions about influences on clinical and public health outcomes, no single study can provide a decisive answer. The perfect study—a large, diverse, well-conducted trial randomizing all relevant versions of a treatment and comprehensively tracking all relevant health outcomes—is never feasible. Instead, we must draw conclusions by piecing together evidence from multiple imperfect studies. A systematic framework for combining disparate, complementary sources of evidence is emerging. We introduce this framework, called evidence triangulation; summarize key approaches based on delineating likely biases due to confounding, measurement, and selection; and review some methods for combining evidence. We illustrate the issues using the example of estimating the effects of alcohol use on dementia. The central tenet of evidence triangulation is to identify the most important weaknesses for any given study approach (and for each specific study applying that approach) and, if necessary, to identify which new sources of evidence that do not share these weaknesses are required. Almost certainly, the new studies will have weaknesses, but when results are consistent across studies that rest on different assumptions, and for which biases should be unrelated, the conclusions are on much sturdier ground.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"72 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survey sampling design in wave 1 of the Global Flourishing Study","authors":"R. Noah Padgett, Richard G. Cowden, Manas Chattopadhyay, Ying Han, John Honohan, Zacc Ritter, Rajesh Srinivasan, Byron R. Johnson, Tyler J. VanderWeele","doi":"10.1007/s10654-024-01167-9","DOIUrl":"https://doi.org/10.1007/s10654-024-01167-9","url":null,"abstract":"<p>The Global Flourishing Study (GFS) is an international collaboration to develop a publicly accessible data resource to promote global research on human flourishing. These data include over 200,000 participants from 22 geographically and culturally diverse countries and one territory designed to be nationally representative of the adult population. The GFS is intended as a longitudinal panel study with recruitment and empanelment for Wave 1 occurring between April 2022 and December 2023. Future waves of data collection will invite participants to complete a survey annually. The annual survey covers a robust set of measures on well-being, health, social, economic, political, religious, spiritual, psychological and demographic variables. The current paper describes the sampling methodology and weighting approaches used to project the samples to be nationally representative. Details are provided on interviewer training and data collection, probability and non-probability samples, creating weights, design effects, and future data collection stages.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"27 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of salt substitution on cumulative blood pressure: a secondary analysis of the SSaSS","authors":"Xiaoxia Li, Liping Huang, Bo Zhou, Zhifang Li, Jixin Sun, Yan Yu, Hongyi Song, Maoyi Tian, Xuejun Yin, Bruce Neal, Yuhong Zhang, Yangfeng Wu, Yi Zhao","doi":"10.1007/s10654-025-01216-x","DOIUrl":"https://doi.org/10.1007/s10654-025-01216-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>The effect of a potassium-enriched salt substitute on cumulative blood pressure (BP) remains unclear. This study aimed to assess the long-term effects of a potassium-enriched salt substitute versus regular salt on cumulative and conventional measures of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP). We analyzed data from the Salt Substitute and Stroke Study (SSaSS), a 5-year cluster randomized controlled trial in rural of China with 20,995 participants. The intervention used salt substitute; controls used regular salt. BP was measured for all participants at baseline, among subsamples at 12-month intervals, and for all alive at 60 months. Cumulative BP was calculated as the average between baseline and follow-up measures multiplied by the time between them (mmHg × year). Linear mixed models were used to assess the effects of salt substitution on BP outcomes at each follow-up visit. After a mean 4.74 years of follow-up, salt substitute compared to the regular salt lowered the cumulative SBP with a mean (SD) of 740 (85) vs. 750 (87) mmHg×year. Salt substitute also lowered cumulative MAP and PP, with means (SD) of 560 (58) vs. 566 (59) mmHg×year, and 306 (67) vs. 313 (68) mmHg×year, respectively. Similar beneficial effects of the salt substitute were observed for traditional measurements of SBP, MAP, and PP. There was no difference in either cumulative DBP (434 vs. 437 mmHg × year) or traditional DBP (85 vs. 86 mmHg). Salt substitute significantly reduced cumulative and traditional SBP, MAP, and PP, but not DBP.</p><h3 data-test=\"abstract-sub-heading\">Trial registration</h3><p>SSaSS ClinicalTrials.gov number: NCT0 2,092,090.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"37 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy in the Swedish national patient register: a review including diagnoses in the outpatient register","authors":"Åsa H. Everhov, Thomas Frisell, Mehdi Osooli, Hannah L. Brooke, Hanne K. Carlsen, Karin Modig, Karl Mårild, Jonathan Lindström, Karin Sköldin, Mona Heurgren, Jonas F. Ludvigsson, Ola Olén","doi":"10.1007/s10654-025-01221-0","DOIUrl":"https://doi.org/10.1007/s10654-025-01221-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>The Swedish National Patient Register (NPR) is an important source of data for epidemiological research. A review in 2010 described the validity of recorded diagnoses for inpatient care, but did not include specialised outpatient care.</p><h3 data-test=\"abstract-sub-heading\">Method</h3><p>Using systematic searches of medical literature databases (Embase, Medline), and reports from members of the Swedish Epidemiological Association, we aimed to identify all studies validating diagnoses and procedure codes in inpatient care since 2010 and all studies validating specialised outpatient care. In addition, we summarize findings from register validation work performed by the National Board of Health and Welfare.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The literature search and personal reports generated 3990 non-duplicate original studies, of which 89 were deemed relevant. Compared to data in patient charts (reference), the median positive predictive value (PPV) for diagnostic codes in the NPR was 84% (interquartile range 72–93%), but with clear differences between types of diagnoses. The median PPV for surgical procedures was 97% (86–99%). The median sensitivity of diagnoses and procedures compared to other registers and cohorts was 73% (45–80%). The completeness of the register has improved over time. Missingness originates mainly from underreporting of procedures performed by private healthcare providers, and for certain variables, e.g. medication codes.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The NPR has good diagnostic accuracy for most diagnoses and very good for surgical procedures. The sensitivity is lower. Longitudinal comparisons of incidence or prevalence are affected by changes in completeness. Missingness is low, although it is higher among private healthcare providers and for specific variables such as drug administration.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of childhood traumatic brain injury on educational attainment in Finland from 1998 to 2018: a retrospective register-based nationwide cohort study","authors":"Julius Möttönen, Ilari Kuitunen, Ville T. Ponkilainen, Ville M. Mattila","doi":"10.1007/s10654-025-01218-9","DOIUrl":"https://doi.org/10.1007/s10654-025-01218-9","url":null,"abstract":"<p>Pediatric traumatic brain injury (pTBI) can lead to considerable mortality, morbidity, mental impairment, and physical disability over time. The direct impact of pTBI on educational attainment is unclear. We included all pediatric 0- to 17-year-old patients who were at least 26 years old at the end of the follow-up with a diagnosis of TBI in the Finnish Care Registry for Health Care (years 1998 to 2018) to form our study group (pTBI group). The reference group comprised patients with ankle and wrist fractures. The pTBI group was further divided into concussions and specific intracranial injuries. We compared this information to Statistics Finland´s Degree/Qualification data to evaluate educational attainment at 3 main levels. All comparisons were made using logistic regression with 95% confidence intervals (CI). The pTBI group comprised 8 487 patients and the reference group comprised 15,552 patients. In total, 7594 pTBI patients had a concussion and 892 a specific intracranial injury. The pTBI group had lower odds of attaining any tertiary education compared with the reference group (odds ratio [OR] 0.85; CI 0.80, 0.90). The pTBI group was also more likely to remain at a lower tertiary education than attain higher tertiary education (OR 0.81; CI 0.74, 0.87). Patients with specific intracranial injuries were more likely not to attain any tertiary education compared to patients with concussions (OR 0.78; CI 0.68, 0.90). People with pTBI had lower educational attainment at all higher educational levels than the reference population with ankle and wrist injuries.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"25 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generalizability of trial criteria on amyloid-lowering therapy against Alzheimer’s disease to individuals with mild cognitive impairment or early Alzheimer’s disease in the general population","authors":"Jacqueline J. Claus, Ilse vom Hofe, Annekee van Ijlzinga Veenstra, Silvan Licher, Harro Seelaar, Frank J. de Jong, Julia Neitzel, Meike W. Vernooij, M. Arfan Ikram, Frank J. Wolters","doi":"10.1007/s10654-025-01220-1","DOIUrl":"https://doi.org/10.1007/s10654-025-01220-1","url":null,"abstract":"<p>Treatment with anti-amyloid-β monoclonal antibodies slowed cognitive decline in recent RCTs in patients with mild cognitive impairment (MCI) and early dementia due to Alzheimer’s disease (AD). However, stringent trial eligibility criteria may affect generalisability to clinical practice. We extracted eligibility criteria for trials of aducanumab, lecanemab and donanemab, and applied these to participants with MCI and early clinical AD dementia from the population-based Rotterdam Study. Participants underwent questionnaires, genotyping, brain-MRI, cognitive testing, and cardiovascular assessment. We determined amyloid status using a validated prediction model based on age and <i>APOE-g</i>enotype. Of 968 participants (mean age: 75 years, 56% women), 779 had MCI and 189 dementia. Across trials, around 40% of participants would be ineligible because of predicted amyloid negativity. At least one clinical exclusion criterion was present in 76.3% of participants for aducanumab, 75.8% for lecanemab, and 59.8% for donanemab. Common criteria were cardiovascular disease (35.2%), anticoagulant (31.2%), psychotropic or immunological medication use (20.4%), anxiety or depression (15.9%), or lack of social support (15.6%). One-third were ineligible based on brain-MRI findings alone, similar across trials and predominantly due to cerebral small-vessel disease. Combining amyloid, clinical, and imaging criteria, eligibility ranged from 9% (95% CI:7.0-11.1) for aducanumab, 8% (6.2–9.9) lecanemab to 15% (12.4–17.5) for donanemab. Findings from recent RCTs reporting protective effects of monoclonal antibodies against amyloid-β are applicable to less than 15% of community-dwelling individuals with MCI or early AD. These findings underline that evidence for drug efficacy and safety is lacking for the vast majority of patients with MCI/AD in routine clinical practice.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"183 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of childhood and adult height on later life cardiovascular disease risk estimated through Mendelian randomization","authors":"Tom G. Richardson, Helena Urquijo, Laurence J. Howe, Gareth Hawkes, John DePaolo, Scott M. Damrauer, Timothy M. Frayling, George Davey Smith","doi":"10.1007/s10654-025-01203-2","DOIUrl":"https://doi.org/10.1007/s10654-025-01203-2","url":null,"abstract":"<p>Taller individuals are at elevated and protected risk of various cardiovascular disease endpoints. Whether this is due to a direct consequence of their height during childhood, a long-term effect of remaining tall throughout the lifecourse, or confounding by other factors, is unknown. We sought to address this by harnessing human genetic data from the UK Biobank to separate the independent effects of childhood and adulthood height using an approach known as lifecourse Mendelian randomization (MR). Protective effects of taller childhood height on risk of later life coronary artery disease (OR = 0.78 per change in height category, 95% CI = 0.70 to 0.86, <i>P</i> = 4 × 10^− 10) and stroke (OR = 0.93, 95% CI = 0.86 to 1.00, <i>P</i> = 0.03) using data from large-scale consortia were found using a univariable model, although evidence of these effects attenuated in a multivariable setting upon accounting for adulthood height. In contrast, direct effects of taller childhood height on increased risk of later life atrial fibrillation (OR = 1.61, 95% CI = 1.42 to 1.79, <i>P</i> = 5 × 10^− 7) and thoracic aortic aneurysm (OR = 1.55, 95% CI = 1.16 to 1.95, <i>P</i> = 0.03) were found even after accounting for adulthood height. Evidence for both of these direct effects was replicated in the Million Veterans Program. The protective effect of childhood height on risk of coronary artery disease and stroke can be largely explained by taller children typically becoming taller individuals in later life. Conversely, the independent effect of childhood height on increased risk of atrial fibrillation and thoracic aortic aneurysm may point towards developmental mechanisms in early life which confer a lifelong risk on these disease outcomes.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"33 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of the pandemic on non-COVID-19 causes of death in the United States: a multiple cause of death analysis","authors":"Yu Li, Hang Li, Tim Adair","doi":"10.1007/s10654-025-01214-z","DOIUrl":"https://doi.org/10.1007/s10654-025-01214-z","url":null,"abstract":"<p>Multiple cause of death data allow for a more granular analysis of the pandemic’s impact on mortality from non-COVID-19 causes of death compared with analysis of a single underlying cause of each death because they are often a co-morbidity of COVID-19. This study estimates excess mortality in the US of non-COVID-19 causes measured as a multiple cause (reported anywhere on the death certificate). Death registration data were used to conduct Poisson regressions of 24 non-COVID-19 causes to estimate expected age-standardized death rates and excess mortality in 2020–21, including by place of death. The ratio of COVID-19 mortality (as underlying or contributing cause) to excess mortality of each non-COVID-19 cause was calculated. During 2020–21, 21 of 24 non-COVID-19 causes exhibited excess mortality, highest for pneumonia (males 126.5%; 95% confidence interval 116.6–136.9%), other respiratory diseases (males 45.2%; 42.2–48.2%), other kidney diseases (males 45.0%, 37.8–52.0%), diabetes (females 38.3%, 32.8–43.4%) and hypertensive heart disease (females 28.9%, 22.8–33.9%). Suicide and influenza mortality was lower than expected. The ratio of COVID-19 (underlying cause) to excess mortality was 74.2% (69.2–79.7%) for men and 68.7% (63.5–75.0%) for women, was significantly higher for hospital (over 90%) than home (less than 16%) deaths and varied greatly between causes. The pandemic led to excess mortality for almost all non-COVID-19 causes in the US when measured as a multiple cause, being particularly high in several non-communicable diseases that increase the risk of dying from COVID-19. COVID-19 appears underreported for home deaths due to its low ratio to excess mortality in this setting.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"183 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of first-time major lower extremity amputations– A Danish Nationwide cohort study from 2010 to 2021","authors":"Anna Trier Heiberg Brix, Katrine Hass Rubin, Tine Nymark, Hagen Schmal, Martin Lindberg-Larsen","doi":"10.1007/s10654-025-01210-3","DOIUrl":"https://doi.org/10.1007/s10654-025-01210-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Aim</h3><p>Major lower extremity amputations (MLEA) are common procedures. Potential changes in surgical strategy and patient characteristics over time have not been described previously. The aim of this study was to investigate the incidence rates and surgical strategies of first-time MLEAs over time from 2010 to 2021. Furthermore, to describe patient demographics, and their changes in the same period.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This is an observational nationwide register study including all first-time MLEAs performed in patients ≥ 18 years from 2010 to 2021, with data from the Danish National Patient Register.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 12,672 first-time MLEA patients were identified from 2010 to 2021. The annual number of first-time MLEAs each year was unchanged at approx. 1000 annually during the study period. In 2021 the total incidence was 21.3/100,000 inhabitants and the total adjusted incidence rate decreased by 2.3% (95% CI 1.8–2.8) per year. The adjusted frequency of transfemoral amputations increased significantly with 10.9% each year confidence interval (CI) (9.7–12.0), whereas knee disarticulation(-19.4%/year CI (-22.2- -16.5)) and transtibial amputation (-7.3%/year CI (-8.5- -6.1)) significantly decreased. The frequency of primary hip disarticulations were stable throughout the study period (p-value 0.06). When analyzing patient comorbidity profiles we found no major changes over time. When statistically testing for time trends, only dyslipidemia (5.7%/year CI (4.5–7.1)), renal insufficiency (1.8%/year CI(0.2–3.3), peripheral artrial disease (-9.3%/year CI (-10.8- -7.7)) and cardiovascular disease (-3.4%/year CI(-4.6- -2.1)) showed a significant time trend in the study period.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>We observed a decreasing incidence of first-time MLEA in Denmark and a shift towards increased use of transfemoral amputations as initial MLEA level. Investigation of the comorbidity profile of MLEA patients revealed some time trend changes during the study period, but with limited clinical relevance. Hence, the observed prominent shift towards a more proximal first time amputation level in Denmark did not seem to be associated with an altered comorbidity profile of these patients. Whether the change in surgical strategy is to the benefit of the patients should be investigated further.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"3 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of effect modifiers using a stratified Mendelian randomization algorithmic framework","authors":"Alice Man, Leona Knüsel, Josef Graf, Ricky Lali, Ann Le, Matteo Di Scipio, Pedrum Mohammadi-Shemirani, Michael Chong, Marie Pigeyre, Zoltán Kutalik, Guillaume Paré","doi":"10.1007/s10654-025-01213-0","DOIUrl":"https://doi.org/10.1007/s10654-025-01213-0","url":null,"abstract":"<p>Mendelian randomization (MR) is a technique which uses genetic data to uncover causal relationships between variables. With the growing availability of large-scale biobank data, there is increasing interest in elucidating nuances in these relationships using MR. Stratified MR techniques such as doubly-ranked MR (DRMR) and residual stratification MR have been developed to identify nonlinearity in causal relationships. These methods calculate causal estimates within strata of the exposure adjusted to mitigate the impact of collider bias. However, their application to scenarios using a stratifying variable other than the exposure to identify the presence of effect modifiers has been limited. The reliable identification of effect modifiers is key to identifying subgroups of patients differentially affected by risk and protective factors. In this study, we present a stratified MR algorithm capable of identifying effect modifiers of causal relationships using adapted forms of DRMR and residual stratification MR. Through simulations, the algorithm was found to be robust at handling nonlinear relationships and forms of collider bias, accommodating both binary and continuous outcomes. Application of the stratified MR algorithm to 1,715 exposure-stratifying variable-outcome combinations identified two Bonferroni significant effect modifiers of causal relationships in the UK Biobank. The causal effect of body mass index on type 2 diabetes mellitus was attenuated with age, while the effect of LDL cholesterol on coronary artery disease was exacerbated with increased serum urate. Overall, we introduce a tool for detecting effect modifiers of causal relationships, and present two cases with clinical implications for personalized risk assessment of cardiometabolic diseases.</p>","PeriodicalId":11907,"journal":{"name":"European Journal of Epidemiology","volume":"17 2 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}