Causal effects of cardiovascular health on five epigenetic clocks

Clinical Epigenetics, Journal Year: 2024, Volume and Issue: 16(1)

Published: Sept. 27, 2024

Language: Английский

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Triangulating Evidence for Antihypertensive Drug Class Efficacy on Cardiovascular and Metabolic Outcomes Using Mendelian Randomisation and Colocalisation

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

Abstract Background Current hypertension treatment guidelines typically recommend a standardised approach, which may not account for the inter-individual variability in blood pressure (BP) response or complex causation of hypertension. This study aims to investigate heterogeneity responses broad range antihypertensive drugs across various cardiometabolic and renal outcomes. Methods employed an integrative approach combining Mendelian randomisation (MR), summary-based MR (SMR), colocalisation analyses impact BP lowering efficacy seventeen drug classes on risk coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), ischemic stroke, chronic kidney (CKD), type 2 diabetes (T2D). Genetic association gene expression summary data were obtained from largest European ancestry GWAS GTEx v8 29 tissues that broadly relevant pathophysiology cardiovascular outcomes included. Results The genetic evidence supported lower SBP was universally beneficial, causally associated with reduced risks all studied genetically predicted varied significantly depending class, revealing their different health Novel associations identified, including protective effects endothelin receptor antagonists, sGC stimulators, PDE5 inhibitors against CAD (per 10-mmHg decrease SBP, OR = 0.197 - 0.348) stroke (OR 0.218 0.686); stimulators CKD 0.532 0.55). SMR include GUCY1A3 MI risk, KCNH2 AF PDE5A risk. Conclusions Our results support potential differential impacts outcomes, underscoring personalised therapy. Future research should validate these findings diverse populations explore mechanistic pathways between modulation Clinical Perspective What is New? utilised randomisation, MR, 17 Although beneficial reducing effectiveness varies by showing Newer therapies, ERAs, inhibitors, showed significant ERAs benefiting AF, CAD, MI, stroke; protecting except T2D; being effective T2D, CKD. are Implications? Understanding varying can guide more strategies, potentially improving patient These only clinical relevance existing therapies but also highlight new therapeutic targets, such as , further exploration. focus validating refine management strategies implement practice.

Language: Английский

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Single cell variant to enhancer to gene map for coronary artery disease

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most disease-associated lie within non-coding regions the genome, rendering it difficult to determine downstream causal gene and cell type. Here, we performed paired single nucleus expression chromatin accessibility profiling from 44 human arteries. To link molecular traits, developed a meta-map 88 samples discovered 11,182 single-cell quantitative trait loci (caQTLs). Heritability enrichment analysis variant mapping demonstrated that smooth muscle cells (SMCs) harbor greatest genetic risk for CAD. capture continuum SMC states disease, used dynamic caQTL modeling first time tissue uncover QTLs whose effects are modified by state expand our insight into regulation heterogenous populations. Notably,

Language: Английский

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The Genetic Variants Influencing Hypertension Prevalence Based on the Risk of Insulin Resistance as Assessed Using the Metabolic Score for Insulin Resistance (METS-IR)

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12690 - 12690

Published: Nov. 26, 2024

Insulin resistance is a major indicator of cardiovascular diseases, including hypertension. The Metabolic Score for Resistance (METS-IR) offers simplified and cost-effective way to evaluate insulin resistance. This study aimed identify genetic variants associated with the prevalence hypertension stratified by METS-IR score levels. Data from Korean Genome Epidemiology Study (KoGES) were analyzed. was calculated using following formula: ln [(2 × fasting blood glucose (FBG) + triglycerides (TG)) body mass index (BMI)]/ [high-density lipoprotein cholesterol (HDL-C)]. participants divided into tertiles 1 (T1) 3 (T3) based on their scores. Genome-wide association studies (GWAS) performed hypertensive cases non-hypertensive controls within these tertile groups logistic regression adjusted age, sex, lifestyle factors. Among groups, 3517 19,774 (17.8%) at T1 had hypertension, whereas 8653 20,374 (42.5%) T3 A total 113 single-nucleotide polymorphisms (SNPs) reached GWAS significance threshold (

Language: Английский

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Cell type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures

Cell Genomics, Journal Year: 2024, Volume and Issue: unknown, P. 100701 - 100701

Published: Dec. 1, 2024

Language: Английский

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