Publications by authors named "Paul de Vries"
Article Synopsis
- The study examines the relationship between polygenic scores for coronary heart disease (CHD) and coronary artery calcium (CAC) in adults aged 75 and older, suggesting that genetic factors may influence arterial aging beyond traditional risk factors.
- Researchers analyzed data from 1,865 participants, finding that higher polygenic CHD risk scores were associated with significantly lower odds of having no CAC and much higher odds of having high CAC levels.
- Each standard deviation increase in the polygenic risk score corresponded to a 78% increase in CAC scores, indicating a strong link between genetic predisposition and arterial health in older adults.
Article Synopsis
- Whole genome sequencing (WGS) helps identify rare genetic variants that may explain the missing heritability of coronary artery disease (CAD) by analyzing 4,949 cases and 17,494 controls from the NHLBI TOPMed program.
- The study estimates that the heritability of CAD is around 34.3%, with ultra-rare variants contributing about 50%, especially those with low linkage disequilibrium.
- Functional annotations show significant enrichment of CAD heritability, highlighting the importance of ultra-rare variants and specific regulatory mechanisms in different cells as major factors influencing genetic risk for the disease.
Article Synopsis
- Researchers aimed to find new genetic variants that are linked to both fibrinogen and C-reactive protein (CRP) by conducting a bivariate genome-wide association study (GWAS).
- The study analyzed data from over 480,000 participants to identify 87 shared genetic loci, including 58 new ones, that are associated with fibrinogen and CRP levels.
- The findings indicate significant overlap between the genetic factors affecting fibrinogen and CRP, suggesting they may share a common genetic architecture.
Article Synopsis
- * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
- * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
Article Synopsis
- Genetic studies have highlighted the need for more diverse research on plasma fibrinogen levels, as previous studies largely focused on Europeans, leading to gaps in understanding and missing heritability.
- By analyzing data from whole-genome sequencing and genotype data from large cohorts, researchers identified 18 genetic loci related to fibrinogen levels, some of which are more common in African populations and include variants that may impact protein function.
- The study's findings indicate a connection between fibrinogen levels and various health conditions, emphasizing the importance of whole-genome sequencing in discovering genetic factors in diverse populations and enhancing knowledge about fibrinogen regulation.
The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bβ, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric "dimer of trimers" (AαBβγ). Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein.
View Article and Find Full Text PDFAlthough both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.
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- Coronary artery calcification (CAC) is linked to heart disease and assessed through a genome-wide association study (GWAS) involving 22,400 participants from various backgrounds.
- The study confirmed connections with four known genetic loci and discovered two new loci related to CAC, with supportive replication findings for both.
- Functional tests suggest that ARSE promotes calcification in vascular smooth muscle cells and its variants may influence CAC levels, identifying ARSE as a key target for potential treatments in vascular calcific diseases.
Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.
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- The study aimed to find genetic risk factors for cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) through a genome-wide association approach.
- Out of 49,230 T2D participants, 8,956 experienced incident CVD events, revealing three new genetic loci associated with increased CVD risk and confirming five known coronary artery disease variants.
- The findings suggest both novel and established genetic factors contribute to CVD risk in T2D patients, highlighting the importance of genetic screening in this population.
There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework.
View Article and Find Full Text PDFAlthough both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.
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- * Discovery of 7 new genetic loci associated with FVIII and 1 new locus for VWF, supporting their roles in thrombotic outcomes via Mendelian randomization.
- * Functional testing revealed that silencing genes like B3GNT2 and CD36 impacted FVIII and VWF release from endothelial cells, indicating their potential regulatory roles.
Article Synopsis
- - The study investigates how the DASH diet score influences systolic blood pressure (BP) in relation to genetic factors, analyzing data from over 127,000 participants from different population groups, primarily European.
- - Researchers identified several genetic loci associated with interactions between an individual's genetics and their response to the DASH diet, particularly focusing on the variant rs117878928 at chromosomal location 15q25.1.
- - Results suggest significant gene-DASH diet interactions affecting systolic BP, highlighting the need for further research in larger, more diverse populations to confirm these findings.
Article Synopsis
- The study focuses on apparent treatment-resistant hypertension (aTRH), defined by the need for four or more antihypertensive medications to control blood pressure in individuals.
- Researchers analyzed genetic data from 12 cohorts using whole-genome sequencing, comparing aTRH cases to normotensive controls and treatment-responsive patients.
- A significant genetic variant linked to hypertension was identified, and further validation of these results in larger and more diverse populations is necessary to understand its potential role in aTRH.
Article Synopsis
- Scientists studied a medicine called r-tPA that helps treat strokes but can cause bleeding in the brain, making things worse for patients.
- They looked at certain genetic factors in the body that might affect this bleeding risk after using r-tPA.
- They found some specific genes that are linked to both blood clotting factors and the risk of bleeding, which could help in understanding how to treat patients better in the future.
Article Synopsis
- Educational attainment is linked to cardiovascular health, and a large genomic study examined how it interacts with cholesterol and triglyceride levels in nearly 226,315 individuals across five population groups.
- The study identified 18 new genetic variations related to lipid levels—nine for low-density lipoprotein (LDL), seven for high-density lipoprotein (HDL), and two for triglycerides (TG)—some of which interact with educational attainment.
- Researchers also found five gene targets that potentially interact with FDA-approved drugs, suggesting a connection between genetics and drug responses related to lipid metabolism and overall health.
Background: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.
Methods: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program.
Article Synopsis
- The study investigated how genetic variations (genotype) interact with dietary habits (specifically the DASH diet score) to influence systolic blood pressure (SBP).
- Researchers analyzed a massive dataset of genetic information from over 127,000 individuals to identify specific genetic locations (loci) that may play a role in this interaction.
- They found significant genetic interactions with the DASH diet score, especially at a specific gene location (rs117878928), indicating that diet can affect blood pressure differently based on an individual's genetic makeup, which highlights the need for further research with more diverse populations.
Article Synopsis
- Large-scale whole-genome sequencing (WGS) studies have enhanced our understanding of how rare genetic variants affect complex human traits through better analysis techniques.* -
- Current methods for analyzing multiple traits are limited in their ability to handle rare variants in large WGS datasets, prompting the development of MultiSTAAR.* -
- MultiSTAAR enables more powerful analysis by considering relatedness, population structure, and the correlation between traits, leading to the discovery of new genetic associations in lipid traits that single-trait analyses missed.*
Article Synopsis
- The CHARGE Gene-Lifestyle Interactions Working Group is exploring how gene-environment interactions affect complex traits and has initiated large-scale studies to enhance statistical power and findings.
- A new screening method, akin to Mendelian randomization, has been developed to identify genomic interactions related to lifestyle factors like smoking and alcohol consumption on serum lipid levels.
- The research found that such interactions contribute significantly to genetic variation, estimating that they account for 1.76% to 14.05% of the heritability of serum lipids, enhancing our understanding of genetic and environmental influences on complex traits.