Publications by authors named "Abbas Dehghan"
Several cardiovascular traits and diseases co-occur with Alzheimer's disease. We mapped their shared genetic architecture using multi-trait genome-wide association studies. Subsequent fine-mapping and colocalisation highlighted 16 genetic loci associated with both Alzheimer's and cardiovascular diseases.
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- MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in regulating gene expression and may serve as biomarkers for various diseases through their presence in plasma.
- The study analyzed 2083 plasma circulating miRNAs from participants in the Rotterdam Study, uncovering 3292 associations between SNPs and miRNAs, with a significant portion confirmed in further studies.
- Findings suggest that specific miRNAs can influence a range of clinical conditions, with miR-1908-5p showing a protective effect against benign colon neoplasm, highlighting the potential for miRNA-targeted therapies in medicine.
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- Genetic research on Alzheimer's disease (AD) has largely concentrated on amyloid-β (Aβ), while this study focuses on understanding the genetic basis of tau pathology to uncover new pathways related to AD.
- A genome-wide association study (GWAS) was conducted using data from the A4 and ADNI studies to analyze genetic variants linked to tau pathology, finding two significant loci and pinpointing certain genes associated with tau deposition.
- Mendelian randomization analyses suggest that the LRRFIP1 protein may have a causal relationship with tau pathology, while the polygenic risk scores showed strong associations with amyloid pathology but not with tau pathology.
MicroRNAs, crucial in regulating protein-coding gene expression, are implicated in various diseases. We performed a genome-wide association study of plasma miRNAs (ex-miRNAs) in 3,743 Framingham Heart Study (FHS) participants and identified 1,027 ex-miRNA-eQTLs (exQTLs) for 37 ex-miRNAs, with 55% replication in an independent study. Colocalization analyses suggested potential genetic coregulation of ex-miRNAs with whole blood mRNAs.
View Article and Find Full Text PDFObjectives: Maternal self-reported ethnicity is recognised as a risk factor for pre-eclampsia in clinical screening tools and models. This study investigated whether ethnicity is acting as a proxy for genetic variants in this context.
Study Design: A total of 436 women from multi-ethnic backgrounds recruited to two UK observational pregnancy hypertension cohort studies were genotyped.
We investigated the effects of 35 inflammatory cytokines on respiratory outcomes, including COVID-19, asthma (atopic and non-atopic), chronic obstructive pulmonary disease (COPD), and pulmonary function indices, using Mendelian randomization and colocalization analyses. The emerging associations were further explored using observational analyses in the UK Biobank. We found an inverse association between genetically predicted macrophage colony stimulating factor (MCSF), soluble intercellular adhesion molecule-1 (sICAM), and soluble vascular cell adhesion molecule-1 with risk of COVID-19 outcomes.
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- 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.
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- Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
- Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
- The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
Neural EGFL like 1 (NELL-1), is a secreted glycoprotein and stimulates osteogenic cell differentiation and bone mineralization. This study aimed to explore the relationship between NELL-1 and Trabecular Bone Score (TBS) as a novel tool for the evaluation of osteoporosis in an elderly population-based cohort study in Iran. A single-locus analysis was performed on TBS using data from 2,071 participants in the Bushehr Elderly Health (BEH) Program.
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- 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.
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- This study investigates the relationship between plasma proteins and stroke risk specifically in South Asian individuals, utilizing genetic data from the UK Biobank and stroke data from the GIGASTROKE consortium.
- Using advanced statistical methods, researchers identified a potential causal link between the glycoprotein GP6 levels and the likelihood of cardioembolic stroke, showing an odds ratio indicating a significant increase in risk.
- Findings suggest that GP6 may not have the same effect on stroke risk in European populations, highlighting the importance of genetic ancestry in biomedical research.
Article Synopsis
- - Early age at menarche (AAM) may lead to higher carotid artery intima-media thickness (cIMT), which is a sign of early vascular disease, and understanding this relationship could improve prevention and treatment strategies for cardiovascular issues.
- - The study explored how AAM affects various cardiometabolic risk factors like body mass index (BMI) and blood pressure, using genetic analyses to determine these connections.
- - Results indicated that AAM was negatively linked to cIMT and positively linked to cholesterol levels, with BMI and systolic blood pressure identified as partial mediators in this association.
Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown.
View Article and Find Full Text PDFBackground: The effect of Ramadan intermittent fasting (RIF) on the metabolic profile, anthropometry and blood pressure has been investigated in multiple studies. However, it is still unknown to what extent changes in nutrient intakes contribute to these changes.
Methods: This observational study was conducted in London (UK) in 2019.
Variations in serum amino acid levels are linked to a multitude of complex disorders. We report the largest genome-wide association study (GWAS) on nine serum amino acids in the UK Biobank participants (117 944, European descent). We identified 34 genomic loci for circulatory levels of alanine, 48 loci for glutamine, 44 loci for glycine, 16 loci for histidine, 11 loci for isoleucine, 19 loci for leucine, 9 loci for phenylalanine, 32 loci for tyrosine and 20 loci for valine.
View Article and Find Full Text PDFBackground: Statins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated through the interleukin 6 (IL-6) signaling pathway.
Methods: Using the Mendelian randomization (MR) approach followed by multivariable MR analyses, we examined the extent to which the effects of statins on CAD might be mediated through the IL-6 signaling pathway.
Background: The dramatic change in lifestyle associated with Ramadan fasting raises questions about its effect on metabolism and health. Metabolites, as the end product of metabolism, are excellent candidates to be studied in this regard.
Objective: This study aims to investigate the effect of Ramadan fasting on the metabolic profile and risk of chronic diseases.
Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.
Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry.
Objective: The association of cerebrospinal fluid (CSF) protein levels with cognitive function in the general population remains largely unexplored. We performed Mendelian randomization (MR) analyses to query which CSF proteins may have potential causal effects on cognitive performance.
Methods And Analysis: Genetic associations with CSF proteins were obtained from a genome-wide association study conducted in up to 835 European-ancestry individuals and for cognitive performance from a meta-analysis of GWAS including 257,841 European-ancestry individuals.
Background: The impact of elevated systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD) at different stages of life is unclear. We aimed to investigate whether genetically mediated SBP/LDL-C is associated with the risk of CHD throughout life.
Methods And Findings: We conducted a three-sample Mendelian randomization analysis using data from the UK Biobank including 136,648 participants for LDL-C, 135,431 participants for SBP, and 24,052 cases for CHD to assess the effect of duration of exposure to the risk factors on risk of CHD.
Background: Genetic variants in the coding region could directly affect the structure and expression levels of genes and proteins. However, the importance of variants in the non-coding region, such as microRNAs (miRNAs), remain to be elucidated. Genetic variants in miRNA-related sequences could affect their biogenesis or functionality and ultimately affect disease risk.
View Article and Find Full Text PDFBiological pathways between alcohol consumption and alcohol liver disease (ALD) are not fully understood. We selected genes with known effect on (1) alcohol consumption, (2) liver function, and (3) gene expression. Expression of the orthologs of these genes in Caenorhabditis elegans and Drosophila melanogaster was suppressed using mutations and/or RNA interference (RNAi).
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- Genetic studies on plasma fibrinogen levels primarily focused on Europeans, revealing numerous associated regions, but there are gaps in understanding due to missing heritability and representation of non-Europeans.
- The researchers utilized whole genome sequencing (WGS) and array-based genotyping data from large cohorts to identify 18 new genetic loci linked to fibrinogen levels, with some variants more common in African populations.
- The study highlights the importance of WGS in discovering genetic variations across diverse populations, linking fibrinogen polygenic risk scores to increased risk for thrombotic and inflammatory diseases like gout.
Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.
Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry.
Objective: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets.
Design: Bi-directional Mendelian randomisation study.
Setting: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits.