Publications by authors named "Aliki Eleni Farmaki"
Article Synopsis
- 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.
Background: Drug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development.
Methods: Genetic hits for AF and related traits were identified through structured search of MEDLINE.
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.
Article Synopsis
- Common SNPs may account for 40-50% of human height variation, and this study identifies 12,111 SNPs linked to height from a large sample of 5.4 million individuals.
- These SNPs cluster in 7,209 genomic segments, encompassing about 21% of the genome and showing varying densities enriched in relevant genes.
- While these SNPs explain a substantial portion of height variance in European populations (40-45%), their predictive power is lower (10-24%) in other ancestries, suggesting a need for more research to enhance understanding in diverse populations.
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
- Muscle weakness, especially prevalent in older adults, is a public health issue, and grip strength is a key measure to assess it; this study investigates the connection between fat levels (adiposity) and grip strength.
- Analyzing data from nearly 470,786 UK Biobank participants, researchers looked at how various adiposity indicators like BMI and waist circumference relate to grip strength, considering factors such as age and sex.
- Findings indicate that in men, higher BMI and waist circumference are linked to stronger grip strength, while higher body fat percentage and waist-hip ratio are related to weaker grip; these associations appear to diminish with age.
Article Synopsis
- The study investigates how genetic variations influence blood-related traits in two isolated populations from the Mediterranean, focusing on individuals from Crete and the Pomak villages in Greece.
- Researchers performed a genome-wide association scan, identifying five rare non-coding genetic variants significantly impacting blood cell counts and distribution.
- A notable portion of the populations carries harmful mutations in the Haemoglobin Subunit Beta (HBB) gene, with distinct mutations prevalent in each group, highlighting the genetic diversity and its effects on various health-related traits.
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease.
View Article and Find Full Text PDFAims/hypothesis: Excess risks of type 2 diabetes in UK South Asians (SA) and African Caribbeans (AC) compared with Europeans remain unexplained. We studied risks and determinants of type 2 diabetes in first- and second-generation (born in the UK) migrants, and in those of mixed ethnicity.
Methods: Data from the UK Biobank, a population-based cohort of ~500,000 participants aged 40-69 at recruitment, were used.
Article Synopsis
- Scientists studied people's genetics to learn about traits related to blood sugar, which helps diagnose and monitor type 2 diabetes.
- Most of the earlier studies only looked at people with European backgrounds, but this research included many more individuals from different backgrounds, finding 242 important genetic spots linked to blood sugar levels.
- By studying a diverse group of people, they discovered new insights about how diabetes works in the body, helping to uncover different biological processes for each glycemic trait.
Homozygosity for the Z allele causes α-antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on nonrespiratory phenotypes, and on lung function in the general population, remain unclear. We conducted a large, population-based study to determine Z allele effects on >2400 phenotypes in the UK Biobank (N=303 353).
View Article and Find Full Text PDFWe investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank ( = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal volume (HV), white matter hyperintensity volume (WMHV), and Alzheimer dementia (AD).
View Article and Find Full Text PDFAim: To understand the relationship between HbA1c and brain health across the entire glycaemic spectrum.
Materials And Methods: We used data from the UK Biobank cohort consisting of 500,000 individuals aged 40-69 years. HbA1c and diabetes diagnosis were used to define baseline glycaemic categories.
Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.
View Article and Find Full Text PDFIntroduction: Diabetes is observed to increase cancer risk, leading to hypothesized direct effects of either hyperglycemia or medication. We investigated associations between glycosylated hemoglobin (HbA1c) across the whole glycemic spectrum and incidence of 16 cancers in a population sample with comprehensive adjustment for risk factors and medication.
Research Design And Methods: Linked data from the UK Biobank and UK cancer registry for all individuals with baseline HbA1c and no history of cancer at enrollment were used.
The present study describes the geographically isolated Pomak population and its particular dietary patterns in relationship to cardiovascular risk factors. We collected a population-based cohort in a cross-sectional study, with detailed anthropometric, biochemical, clinical, and lifestyle parameter information. Dietary patterns were derived through principal component analysis based on a validated food-frequency questionnaire, administered to 1702 adult inhabitants of the Pomak villages on the Rhodope mountain range in Greece.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFBody-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants.
View Article and Find Full Text PDFArticle Synopsis
- Very low-depth sequencing is a promising, cost-effective method for analyzing rare genetic variations in complex traits, but its genotype quality and analytical power still need thorough investigation.
- In a study involving 1,239 individuals from an isolated population, researchers established a reliable process for calling and imputing genotypes from very low-depth whole-genome sequencing, achieving high concordance with traditional high-depth methods.
- The findings revealed that 1× depth sequencing could identify a greater number of true low-frequency variants and produced more significant association signals for quantitative traits compared to conventional genotyping approaches.
Article Synopsis
- The original article had a mistake in Fig. 2, where the labels "rare" and "common" were switched.
- This error has been fixed in both the PDF and HTML formats of the article.
- Readers can now find the correct information in the updated versions.
Article Synopsis
- The study investigates the impact of rare genetic variants on six cardiometabolic traits by analyzing the genomes of 1457 individuals from an isolated population.
- It identifies significant rare regulatory variations that influence traits, separate from known common genetic signals.
- Notably, the research highlights a connection between rare variants in the gene FAM189B and triglyceride levels, emphasizing its potential role in lipid metabolism.