The Polygenic Score - Rare Variant Causal Pivot: A Conditional Approach to Discovery in Complex Disease Genetics DOI Open Access
Chad A. Shaw,

Christopher Williams,

Tan Tao

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

Abstract We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages one established factor to detect contribution of second suspected cause. Specifically, polygenic risk scores (PRS) serve known causes, while rare variants (RV) or RV ensembles are evaluated candidate causes. incorporates outcome-induced association by conditioning on disease status. derive conditional maximum likelihood procedure binary and quantitative traits develop Likelihood Ratio Test (CP-LRT) signals. Through simulations, we demonstrate CP-LRT’s robust power superior error control compared alternatives. apply CP-LRT UK Biobank (UKB) data, three exemplar diseases: hypercholesterolemia (HC, LDL-c ≥ 4.9 mmol/L; n c =24,656), breast cancer (BC, ICD10 C50; =12,479), Parkinson’s (PD, G20; =2,940). For PRS, utilize UKB-derived values, RVs, analyze ClinVar pathogenic/likely pathogenic loss-of-function mutations disease-relevant genes: LDLR HC, BRCA1 BC, GBA PD. Significant signals were detected all Cross-disease synonymous variant analyses controls. further ancestry adjustment using matching inverse probability weighting, extend examine oligogenic burden lysosomal storage pathway reveals an approach address is extensible method inference discovery genetics.

Язык: Английский

Striving Towards Equity in Cardiovascular Genomics Research DOI Creative Commons

Javier Jurado Vélez,

Nekayla Anderson,

Ivree Datcher

и другие.

Current Atherosclerosis Reports, Год журнала: 2025, Номер 27(1)

Опубликована: Фев. 18, 2025

Язык: Английский

Процитировано

0

Triglyceride/high density lipoprotein cholesterol index and future cardiovascular events in diabetic patients without known cardiovascular disease DOI Creative Commons
Ryosuke Nakashima, Shota Ikeda, Keisuke Shinohara

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 17, 2025

The triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index, calculated as TG divided by HDL-C, has been suggested a predictor of cardiovascular disease (CVD). We investigated the association between TG/HDL-C index and CVD events in type 2 diabetes mellitus (T2DM) patients with retinopathy hyperlipidemia but no known CVD, enrolled EMPATHY study, which compared intensive standard statin therapy (targeting LDL-C levels < 70 mg/dL ≥ 100 to 120 mg/dL, respectively). A total 4665 were into high (TG/HDL-C 2.5, n = 2013) low 2652) groups. During median follow-up 36.8 months, 260 occurred. group had higher risk than (HR 1.89, 95% CI 1.45–2.47, p 0.001). This remained consistent across subgroups. trend toward interaction treatment allocation for was observed (p 0.062). Intensive reduced not group. In conclusion, 2.5 associated T2DM without history CVD. may identify who benefit from treatment.

Язык: Английский

Процитировано

0

Beyond Cholesterol: Emerging Risk Factors in Atherosclerosis DOI Open Access
Makhabbat Bekbossynova, Timur Saliev, T Ivanova-Razumova

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(7), С. 2352 - 2352

Опубликована: Март 29, 2025

Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide, traditionally linked to elevated cholesterol levels, particularly low-density lipoprotein (LDL-C). However, despite aggressive lipid-lowering strategies, residual risk persists, underscoring the need explore additional contributing factors. This review examines emerging factors beyond cholesterol, including chronic inflammation, gut microbiota composition, oxidative stress, environmental exposures. Inflammation plays pivotal role in atherogenesis, with markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) serving indicators disease activity. The microbiome, metabolites like trimethylamine N-oxide (TMAO), has been implicated vascular inflammation plaque development, while beneficial short-chain fatty acids (SCFAs) demonstrate protective effects. Oxidative stress further exacerbates endothelial dysfunction instability, driven by reactive oxygen species (ROS) lipid peroxidation. Additionally, factors, air pollution, heavy metal exposure, endocrine disruptors, psychological have emerged significant contributors disease. Understanding these novel offers broader perspective on atherosclerosis pathogenesis provides new avenues for targeted prevention therapeutic interventions.

Язык: Английский

Процитировано

0

Lipoprotein cholesterol ratios and cardiovascular disease risk in US adults: a cross-sectional study DOI Creative Commons

Xiu‐Ming Yang,

Qiuyun Chen, Qing‐Yu Zhang

и другие.

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Апрель 17, 2025

The ratio of non-high-density lipoprotein cholesterol to high-density (NHHR) has been introduced as a novel indicator evaluate lipid metabolism. study explored the association between NHHR and cardiovascular disease (CVD). A cross-sectional was achieved by utilizing data obtained from NHANES (2003-2016). CVD assessed multivariate logistic regression analysis (LRA) restricted cubic spline (RCS) analysis. Also, interaction tests subgroup analyses were employed explore whether associations differ subgroups. Then, threshold conducted for interval delineation detection effects with two-segment piecewise LR model. cohort 11,471 individuals involved. results indicated that linear relationship not significant (P trend >0.05). RCS revealed non-linear J-shaped risk. model established assess effect NHHR. log-likelihood test < 0.001) suggested exhibited better performances compared single-line Additionally, tangent point occurred at 2.82, likelihood increased 21% one unit (OR = 1.21, 95% CI 1.10-1.34). detected prevalence CVD, suggesting could serve assessment marker identifying high-risk populations. However, further studies are needed confirm this finding.

Язык: Английский

Процитировано

0

Cardiovascular disease risk factors are associated with conventional lipids and apolipoproteins in South African adults of African ancestry DOI Creative Commons
AA Vorster, Ruan Kruger, Catharina M. C. Mels

и другие.

Lipids in Health and Disease, Год журнала: 2025, Номер 24(1)

Опубликована: Май 15, 2025

Although conventional lipids (high density lipoprotein cholesterol (HDLC), low (LDLC), total (TC) and triglycerides (TG)) are therapeutic targets to manage prevent atherosclerotic cardiovascular disease (CVD), apolipoprotein (Apo) levels have sparked interest for their potential improve CVD risk prediction. This study explored the relationships of traditional factors with lipids, as well ApoA1, ApoB its ratio (ApoB: ApoA1) in South African adults ancestry. included 1697 (aged 29 94) from Prospective Urban Rural Epidemiology (PURE) study. The markers body mass index (BMI), physical activity index, tobacco use, dietary fat intake, γ-glutamyl transferase (γGT) glycated haemoglobin (HbA1C). Conventional were measured serum samples using standard methodology, while ApoA1 a multiplex magnetic bead immunoassay. Stratified into tertiles lipid Apo levels, trends emerged across multiple markers, including BMI, γGT HbA1C levels. Higher LDLC, TC, TG, ApoB: along lowest HDLC exhibited higher prevalence Type II diabetes mellitus (all p ≤ 0.024) overweight or obesity except 0.024). was negatively associated TG positively BMI < 0.001) 0.005). Similarly, (β=-0.067 (-0.125; -0.010), = 0.022) (β=-0.071 (-0.122; -0.020), 0.007), (β 0.168 (0.117; 0.218), 0.001). showed positive associations 0.213 (0.163; 0.263), 0.123 (0.074; 0.172), In ancestry, various established suggests that these apolipoproteins may provide additional mechanistic insights beyond understand aetiology early cardiometabolic development.

Язык: Английский

Процитировано

0

Effect of inclisiran on lipid and mechanical vascular profiles in familial hypercholesterolemia subjects: results from a single lipid center real-world experience DOI Creative Commons
Giosiana Bosco,

Francesco Barbagallo,

Maurizio Di Marco

и другие.

Progress in Cardiovascular Diseases, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

Lipoprotein (a) levels and clinical decision-making: data from a Mexican cohort at a tertiary medical institution DOI Creative Commons
Ivette Cruz‐Bautista, Yuscely Flores-Jurado,

Guillermo Roa-Álvarez

и другие.

Lipids in Health and Disease, Год журнала: 2025, Номер 24(1)

Опубликована: Май 26, 2025

Approximately 20% of the global population has a Lp(a) concentrations above 50 mg/dL (> 125nmol/L), yet many remain unaware associated cardiovascular risks. In Mexico, routine measurement is uncommon. This study aimed to investigate frequency testing, and clinical actions taken by physicians upon detecting elevated in patients at tertiary medical institution. Using an algorithm-based screening system, we reviewed biochemical data with measurements from 2019 2024. Data were retrieved laboratory information system electronic health records. Complementary assessment obtained radiology cardiology departments. Of 150,083 individuals evaluated institution, only 830 (0.5%) underwent testing rates increasing 0.037% 0.24% 2023. Elevated mg/dL) found 21% patients, 2.2% had > 180 mg/dL. Patients significantly higher atherosclerotic disease (ASCVD) (p < 0.001) familial hypercholesterolemia 0.004) than those lower levels. Interestingly, diabetes prevalence was 4 (51.5% vs. 33.4%, p 0.001). Despite risk, 26% levels received interventions modify risk factors. infrequent setting. Clinical factors insufficient among Lp(a). These findings highlight need for greater awareness healthcare providers development comprehensive management algorithms mitigate -related risk.

Язык: Английский

Процитировано

0

Association of sdLDL-C/LDL-C ratio with atherosclerotic cardiovascular disease: a case-control study DOI Creative Commons

Yuxin Yang,

Tao Yan, Ya Wang

и другие.

BMC Cardiovascular Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Июнь 3, 2025

Low-density lipoprotein cholesterol (LDL-C) and small dense low-density (sdLDL-C) are key drivers of atherosclerotic cardiovascular disease (ASCVD) risk. This study aims to investigate the correlation between sdLDL-C/LDL-C ratio ASCVD provide new ideas for accurate prediction identifying high-risk groups. The data were derived from patients who visited Affiliated Hospital Inner Mongolia Medical University January 2019 July 2023. relationship odds was analyzed using univariate multivariate logistic regression analysis. Subgroup analysis investigates potential effects age, sex, hypertension heterogeneity, ASCVD. included 8924 subjects with an average age (59 ± 11) years. Multivariate revealed that compared lowest quartile ratio, increased by 1.39, 3.48, 9.34 times in groups 2, 3, 4, respectively (OR values: 2.39 [95% CI 1.91-2.99], 4.48[95% 3.59-5.60], 10.34 8.08-13.22]; P < 0.001). increasing trend also observed stratified analyses sex. An elevated is associated ratio's predictive ability occurrence surpasses sdLDL-C alone.

Язык: Английский

Процитировано

0

The Polygenic Score - Rare Variant Causal Pivot: A Conditional Approach to Discovery in Complex Disease Genetics DOI Open Access
Chad A. Shaw,

Christopher Williams,

Tan Tao

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

Abstract We present the Causal Pivot (CP) as a structural causal model (SCM) for analyzing genetic heterogeneity in complex diseases. The CP leverages one established factor to detect contribution of second suspected cause. Specifically, polygenic risk scores (PRS) serve known causes, while rare variants (RV) or RV ensembles are evaluated candidate causes. incorporates outcome-induced association by conditioning on disease status. derive conditional maximum likelihood procedure binary and quantitative traits develop Likelihood Ratio Test (CP-LRT) signals. Through simulations, we demonstrate CP-LRT’s robust power superior error control compared alternatives. apply CP-LRT UK Biobank (UKB) data, three exemplar diseases: hypercholesterolemia (HC, LDL-c ≥ 4.9 mmol/L; n c =24,656), breast cancer (BC, ICD10 C50; =12,479), Parkinson’s (PD, G20; =2,940). For PRS, utilize UKB-derived values, RVs, analyze ClinVar pathogenic/likely pathogenic loss-of-function mutations disease-relevant genes: LDLR HC, BRCA1 BC, GBA PD. Significant signals were detected all Cross-disease synonymous variant analyses controls. further ancestry adjustment using matching inverse probability weighting, extend examine oligogenic burden lysosomal storage pathway reveals an approach address is extensible method inference discovery genetics.

Язык: Английский

Процитировано

0