Evaluating the impact of modeling choices on the performance of integrated genetic and clinical models DOI Creative Commons
Theodore Morley,

Drew Willimitis,

Michael Ripperger

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

Abstract The value of genetic information for improving the performance clinical risk prediction models has yielded variable conclusions. Many methodological decisions have potential to contribute differential results across studies. Here, we performed multiple modeling experiments integrating and demographic data from electronic health records (EHR) understand which decision points may affect performance. Clinical in form structured diagnostic codes, medications, procedural demographics were extracted two large independent systems polygenic scores (PRS) generated all patients with corresponding biobanks. Crohn’s disease was used as model phenotype based on its substantial component, established EHR-based definition, sufficient prevalence training testing. We investigated impact PRS integration method, well choices regarding sample, complexity, metrics. Overall, our show that including resulted higher by some metrics but gain only robust when combined alone. Improvements inconsistent or negligible after additional information. also varied a small improvement cases combining output (late-fusion) compared inclusion an feature (early-fusion). effects other between institutions though increased more compute-intensive such random forest. This work highlights importance considering interpreting models.

Language: Английский

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations DOI Creative Commons
Niall J. Lennon, Leah C. Kottyan, Christopher Kachulis

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(2), P. 480 - 487

Published: Feb. 1, 2024

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can implemented the clinic, including reduced performance of diverse populations, and interpretation communication genetic results both providers patients. To address these challenges, National Human Genome Research Institute-funded Electronic Medical Records Genomics (eMERGE) Network has developed a framework pipeline for return PRS-based genome-informed assessment 25,000 adults children as part clinical study. From an initial list 23 conditions, ten were selected implementation based on PRS medical actionability potential utility, cardiometabolic diseases cancer. Standardized metrics considered selection process, with additional consideration given strength evidence African Hispanic populations. We then (score transfer laboratory, validation verification score performance), used ancestry calibrate mean variance, utilizing genetically data from 13,475 participants All Us Program cohort train test model parameters. Finally, we created regulatory compliance report inclusion assessment. The experience eMERGE inform approach needed implement testing settings.

Language: Английский

Citations

77
Recent advances in polygenic scores: translation, equitability, methods and FAIR tools DOI Creative Commons
Ruidong Xiang, Martin Kelemen, Yu Xu

et al.

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: Feb. 19, 2024

Abstract Polygenic scores (PGS) can be used for risk stratification by quantifying individuals’ genetic predisposition to disease, and many potentially clinically useful applications have been proposed. Here, we review the latest potential benefits of PGS in clinic challenges implementation. could augment through combined use with traditional factors (demographics, disease-specific factors, family history, etc.), support diagnostic pathways, predict groups therapeutic benefits, increase efficiency clinical trials. However, there exist maximizing utility PGS, including FAIR (Findable, Accessible, Interoperable, Reusable) standardized sharing genomic data needed develop recalculate equitable performance across populations ancestries, generation robust reproducible calculations, responsible communication interpretation results. We outline how these may overcome analytically more diverse as well highlight sustained community efforts achieve equitable, impactful, healthcare.

Language: Английский

Citations

30
A polygenic risk score added to a QRISK®2 cardiovascular disease risk calculator demonstrated robust clinical acceptance and clinical utility in the primary care setting DOI Creative Commons

Ahmet Fuat,

Ella Adlen, Mark Monane

et al.

European Journal of Preventive Cardiology, Journal Year: 2024, Volume and Issue: 31(6), P. 716 - 722

Published: Jan. 19, 2024

The aim of the study was to assess real-world feasibility, acceptability, and impact an integrated risk tool for cardiovascular disease (CVD IRT, combining standard QRISK®2 algorithm with a polygenic score), implemented within routine primary practice in UK National Health Service.

Language: Английский

Citations

12
Long-Term Body Mass Index Variability and Adverse Cardiovascular Outcomes DOI Creative Commons

Zakaria Almuwaqqat,

Qin Hui, Chang Liu

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(3), P. e243062 - e243062

Published: March 21, 2024

Importance Body mass index (BMI; calculated as weight in kilograms divided by height meters squared) is a commonly used estimate of obesity, which complex trait affected genetic and lifestyle factors. Marked gain loss could be associated with adverse biological processes. Objective To evaluate the association between BMI variability incident cardiovascular disease (CVD) events 2 distinct cohorts. Design, Setting, Participants This cohort study data from Million Veteran Program (MVP) 2011 2018 participants UK Biobank (UKB) enrolled 2006 2010. were followed up for median 3.8 (5th-95th percentile, 3.5) years. baseline CVD or cancer excluded. Data analyzed September 2022 2023. Exposure was retrospective SD coefficient variation (CV) using multiple clinical measurements to baseline. Main Outcomes Measures The main outcome composite (incident nonfatal myocardial infarction, acute ischemic stroke, death), assessed Cox proportional hazards modeling after adjustment risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein smoking status, diabetes statin use. Secondary analysis whether associations dependent on polygenic score BMI. Results Among 92 363 US veterans MVP (81 675 [88%] male; [SD] 56.7 [14.1] years), there 9695 Hispanic participants, 22 488 non-Hispanic Black 60 180 White participants. A 4811 observed 2018. CV 16% higher across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These unchanged among subgroups UKB included 65 047 individuals (mean 57.30 (7.77) years; 38 065 [59%] female) had 6934 events. Each 1-SD increase 8% increased death (HR, 1.08; 1.04-1.11). Conclusions Relevance found that veterans, significant marker independent major racial ethnic groups. consistent end point. Further studies should investigate phenotype high variability.

Language: Английский

Citations

12
Dyslipidemia and the Current State of Cardiovascular Disease: Epidemiology, Risk Factors, and Effect of Lipid Lowering DOI Creative Commons
Liam R. Brunham, Eva Lonn, Shamir R. Mehta

et al.

Canadian Journal of Cardiology, Journal Year: 2024, Volume and Issue: 40(8), P. S4 - S12

Published: Aug. 1, 2024

Ischemic heart disease and stroke are the leading causes of death worldwide. Herein we review burden, epidemiology, risk factors for atherosclerotic cardiovascular (ASCVD). The focus this is on current state ASCVD in Canada, however, findings regarding epidemiological trends likely to be reflective global trends, particularly high-income countries, discussion lipid lowering universally applicable. In burden from second only cancer deaths. There major differences related sex, geography, socioeconomic status. have been identified, although new emerging an active area research. Recent developments such as polygenic scores provide potential identify individuals at earlier life institute preventative measures. Dyslipidemia, particular elevated concentrations low-density lipoprotein cholesterol apolipoprotein B a cause ASCVD. Therapies lower lipoprotein/apolipoprotein levels key components treating preventing Addressing causal manner that comprehensively considers clinical, social, economic implications prevention strategies will essential reduce improve outcomes patients.

Language: Английский

Citations

9
Heavy Metals and Cardiovascular Health: Uncovering Links and Health Challenges DOI

Yogita Ozarde,

Dishank Purandare,

S. K. Deshmukh

et al.

Journal of Trace Elements in Medicine and Biology, Journal Year: 2025, Volume and Issue: unknown, P. 127648 - 127648

Published: April 1, 2025

Language: Английский

Citations

0
Utilization of polygenic risk scores in drug development protocols DOI
Michelle A. Pressly, Robert N. Schuck,

Padmaja Mummaneni

et al.

Pharmacogenomics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 5

Published: April 9, 2025

The development of polygenic risk scores (PRSs), which make use genetic testing to assess an individual's developing certain diseases or conditions based on collective variant information, can be applied in drug enrich clinical trials predict response treatment. From querying documents submitted the Food & Drug Administration, landscape PRSs across time shows increased guiding trials. Of trial protocols submitted, most were therapeutic areas neurology, radiology (imaging and diagnostic pharmaceuticals), psychiatry, oncology. Use is frequent early (phase 1, phase 1/2, 3) generally supports secondary exploratory analyses. Additionally, about half developed novel PRSs, other used preexisting PRSs. As researchers, regulators, clinicians aim understand results implications trials, continued despite being less common, reinforces need for further exploration.

Language: Английский

Citations

0
Meta-prediction of coronary artery disease risk DOI
Shang‐Fu Chen, Sang Eun Lee, Hossein Javedani Sadaei

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

Citations

0
An Evidence Map of the Women Veterans’ Health Literature, 2016 to 2023 DOI Creative Commons
Karen M. Goldstein,

Rachel Pace,

Caroline Dancu

et al.

JAMA Network Open, Journal Year: 2025, Volume and Issue: 8(4), P. e256372 - e256372

Published: April 22, 2025

Importance Women veterans are the fastest-growing veteran subpopulation in US. often experience military service–related health issues addition to conditions common all women. Because women more likely receive care civilian setting than through Department of Veterans Affairs (VA), women’s clinicians should be equipped provide patient-centered for veterans. The requires evidence-based informed by population-specific scientific literature. An updated evidence map evaluating veteran–focused literature is needed. Objective To scope and breadth veterans’ published from 2016 2023. Evidence Review In this systematic review, MEDLINE, Embase, CINAHL Complete were searched eligible articles Articles reporting about US outcomes or on providing included. Included required report patient-level that included either data only reported results separately grouped primary focus area based categories previously established VA Women’s Health research agendas prior maps. Findings volume between 2023 932 was double 8 years. largest portion focused chronic medical (137 [15%]), general mental (203 [22%]), interpersonal violence (121 3[13%]). Areas greatest growth reproductive (physical mental), pain, suicide, nonsuicidal self-injury. Additionally, emerging areas inquiry found, including military-related toxic exposures harassment within setting. Conclusions Relevance review veterans, found have doubled expanded important aligned with priorities. However, despite related several gaps remain field study. Research addressing pertinent a growing aging population will require rigorous program evaluations.

Language: Английский

Citations

0
Improved ASCVD Screening in Diabetes: a Focus on Scoring Models and Detection Techniques DOI Creative Commons
Răzvan-Liviu Zanfirescu, Larisa Anghel, Bogdan-Sorin Tudurachi

et al.

Romanian Journal of Internal Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). Diabetes accelerates the progression atherosclerosis through key mechanisms such as insulin resistance, hyperglycemia, dyslipidemia, chronic inflammation, oxidative stress, significantly increasing risk coronary artery disease, stroke, heart failure. Traditional assessment models treatment strategies often fall short fully addressing these complexities, leaving substantial residual diabetic patients. This review focuses on need for enhanced screening protocols populations, examining advanced scoring detection techniques aimed at improving early identification management ASCVD. Also, this study examines pathophysiological links between atherosclerosis, emphasizing protocols. Emerging tools, non-invasive imaging (e.g., calcium scoring, CCTA) biomarkers polygenic scores), offer promise improved stratification. Additionally, newer therapeutic targeting inflammation resistance are being explored to mitigate risks population. Given significant associated diabetes, particularly T2DM, advancements crucial reducing related atherosclerotic events.

Language: Английский

Citations

0