Publications by authors named "Helgadottir A"
Article Synopsis
- Dilated cardiomyopathy (DCM) is a major cause of heart failure, and this study analyzes genetic factors by examining 14,256 DCM cases and 36,203 participants from the UK Biobank for related traits.
- Researchers discovered 80 genomic risk loci and pinpointed 62 potential effector genes tied to DCM, including some linked to rare variants.
- The study uses advanced transcriptomics to explore how cellular functions contribute to DCM, showing that polygenic scores can help predict the disease in the general population and emphasize the importance of genetic testing and development of precise treatments.
Mendelian Randomization studies indicate that BMI contributes to various diseases, but it's unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement.
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- The study aims to investigate the genetic factors associated with accessory atrioventricular pathways (APs) and related heart rhythm disorders using a genome-wide association study (GWAS).
- It involved analyzing genetic data from over 1,200,000 control individuals and 2,310 individuals with APs from multiple countries and various health databases.
- Key findings revealed three significant genetic variants linked to APs, particularly in specific genes (CCDC141 and SCN10A), with implications for understanding conditions like paroxysmal supraventricular tachycardia (PSVT).
Importance: Recurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology are incompletely understood.
Objective: To use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis.
Background: In 2021, the American College of Medical Genetics and Genomics (ACMG) recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available. Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.
Methods: We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings, version 3.
Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single hematopoietic stem cell lineage. Using whole-genome sequencing of 45,510 Icelandic and 130,709 UK Biobank participants combined with a mutational barcode method, we identified 16,306 people with CH. Prevalence approaches 50% in elderly participants.
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- Migraine is a complicated neurovascular condition with varying symptoms, traditionally studied as a single type in genome-wide association studies (GWAS), but this research focuses on two main subtypes: migraine with aura (MA) and migraine without aura (MO).
- The study analyzed large datasets from six European populations, identifying four new gene variants associated with MA and classifying 13 variants for MO, highlighting a significant frameshift variant in PRRT2 linked to MA and epilepsy.
- Additionally, testing on rare variants showed that loss-of-function mutations in SCN11A provide strong protection against migraine, while another variant affecting KCNK5 offers large protection against both migraine and brain aneurysms, suggesting new avenues for treatment.
Many sequence variants have additive effects on blood lipid levels and, through that, on the risk of coronary artery disease (CAD). We show that variants also have non-additive effects and interact to affect lipid levels as well as affecting variance and correlations. Variance and correlation effects are often signatures of epistasis or gene-environmental interactions.
View Article and Find Full Text PDFImportance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain.
Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations.
Design, Setting, And Participants: The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018).
Background: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear.
Methods: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls.
Article Synopsis
- The study aims to uncover new genetic factors linked to calcific aortic stenosis (AS) and identify mechanisms through functional and expression data integration.
- A large genome-wide meta-analysis involving over 653,000 European participants found 17 significant genetic loci associated with AS, with further support for their involvement from independent cohorts.
- Findings highlight the roles of dyslipidemia, inflammation, calcification, and obesity in AS development, suggesting potential new strategies for treatment and prevention.
Article Synopsis
- This study investigates the genetics of syncope, a common medical condition, to improve understanding of its causes and potential outcomes.
- A large-scale analysis of genetic data from over half a million people identified 18 genetic variants linked to syncope, most of which were newly discovered, highlighting the condition's unique genetic traits.
- The findings suggest a relationship between syncope and cardiovascular health, indicating that genetic factors related to heart rate and blood pressure regulation could be involved, reinforcing the need for careful evaluation of patients experiencing syncope.
Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.
Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.
The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci.
View Article and Find Full Text PDFNonalcoholic fatty liver (NAFL) and its sequelae are growing health problems. We performed a genome-wide association study of NAFL, cirrhosis and hepatocellular carcinoma, and integrated the findings with expression and proteomic data. For NAFL, we utilized 9,491 clinical cases and proton density fat fraction extracted from 36,116 liver magnetic resonance images.
View Article and Find Full Text PDFBackground And Aims: The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration.
Method And Results: We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression.
Article Synopsis
- Researchers studied the genetic connections to blood fats using data from 1.6 million people from different backgrounds to understand why certain fats are higher or lower in the body.
- They looked at special genes and how they interact in the liver and fat cells, finding that the liver plays a big part in controlling fat levels.
- Two specific genes, CREBRF and RRBP1, were highlighted as important in understanding how our bodies manage fats due to strong supporting evidence.
Article Synopsis
- Back pain is prevalent and complex, with this study exploring its genetic links through a genome-wide association approach involving nearly 120,000 cases of dorsalgia and about 59,000 of intervertebral disc disorder.
- Researchers identified 41 genetic variants across 33 different locations, with the strongest correlation to a specific variant in the CHST3 gene that impacts intervertebral discs.
- The study highlights that certain rare loss-of-function variants in the SLC13A1 gene may contribute significantly to intervertebral disc disorders, pointing to genetic factors that influence cartilage, bone health, and related inflammatory processes.
Article Synopsis
- Increased blood lipid levels are linked to cardiovascular disease and are influenced by genetics, diet, and medication use globally.
- Despite advancements in treatment, heart disease remains the top cause of death, highlighting the need for continued research.
- A recent multi-ancestry GWAS encompassing 1.65 million individuals, including 350,000 from non-European backgrounds, emphasizes the importance of diverse genetic studies for better understanding lipid levels and improving clinical applications of genetic findings.
Platelets play an important role in hemostasis and other aspects of vascular biology. We conducted a meta-analysis of platelet count GWAS using data on 536,974 Europeans and identified 577 independent associations. To search for mechanisms through which these variants affect platelets, we applied cis-expression quantitative trait locus, DEPICT and IPA analyses and assessed genetic sharing between platelet count and various traits using polygenic risk scoring.
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- The HERMES consortium is focused on understanding the genomic and molecular factors that contribute to heart failure by analyzing data from a large number of studies worldwide.
- It includes 51 studies from 11 countries, gathering data from over 68,000 heart failure cases and nearly 950,000 controls, with broad demographic representation and long follow-up periods.
- The main goals are to identify genetic risk factors for heart failure, explore causal pathways, and create tools to help stratify patients and predict risks based on their genetic information.