Publications by authors named "Gieger C"
Background: Type 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.
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- Distal sensorimotor polyneuropathy (DSPN) is a prevalent neurological condition affecting older adults and those with obesity or diabetes, leading to significant health issues.
- The Interpretable Multimodal Machine Learning (IMML) framework was used to predict the prevalence and incidence of DSPN by analyzing a diverse set of data from over 1,000 participants, including clinical, genomic, and metabolomic information.
- Results showed that while clinical data alone could differentiate DSPN cases, combining it with additional molecular data improved prediction accuracy and identified potential biomarkers related to inflammation and fatty acid metabolism, offering new insights for treatment and prevention strategies.
Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide.
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- This study investigates the link between an epigenetic risk score (ERS) related to alcohol consumption and blood pressure traits, finding significant associations between higher ERS and increased blood pressure levels among participants.
- In the analysis of 3,898 individuals from the Framingham Heart Study, each unit increase in the ERS correlated with a rise in systolic blood pressure (SBP) by almost 2 mm Hg and diastolic blood pressure (DBP) by about 0.68 mm Hg.
- The research suggests that the ERS could serve as a useful tool for assessing cardiovascular risks linked to alcohol consumption, especially in cases where self-reported data may be unreliable.
Aims: A data-driven cluster analysis in a cohort of European individuals with type 2 diabetes (T2D) has previously identified four subgroups based on clinical characteristics. In the current study, we performed a comprehensive statistical assessment to (1) replicate the above-mentioned original clusters; (2) derive de novo T2D subphenotypes in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort and (3) describe underlying genetic risk and diabetes complications.
Methods: We used data from n = 301 individuals with T2D from KORA FF4 study (Southern Germany).
Article Synopsis
- Type 2 diabetes (T2D) and obesity are linked to low levels of natriuretic peptide (NP) and reduced NP guanylyl cyclase receptor-A (GCA) in muscles and fat tissue.
- Research in mice shows that lack of ANP/GCA leads to metabolic issues and prediabetes, causing insulin resistance and poor endurance.
- ANP/GCA is crucial for maintaining mitochondrial function and oxidative capacity in skeletal muscle, suggesting it plays a key role in the development of prediabetes.
Background: Protein biomarkers may contribute to the identification of vulnerable subgroups for premature mortality. This study aimed to investigate the association of plasma proteins with all-cause and cause-specific mortality among individuals with and without baseline type 2 diabetes (T2D) and evaluate their impact on the prediction of all-cause mortality in two prospective Cooperative Health Research in the Region of Augsburg (KORA) studies.
Methods: The discovery cohort comprised 1545 participants (median follow-up 15.
Article Synopsis
- * Results show that four specific single nucleotide polymorphisms (SNPs) in individuals with type 2 diabetes are linked to DSPN, meaning those with certain genetic variations are more likely to experience nerve damage, especially as the criteria for diagnosis become stricter.
- * The findings support the idea that genetic factors related to the metabolism of glucose intermediates play a significant role in the development of diabetic neuropathy, highlighting potential areas for
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- Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
- They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
- Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
Despite extensive research on 5-methylcytosine (5mC) in relation to smoking, there has been limited exploration into the interaction between smoking and 5-hydroxymethylcytosine (5hmC). In this study, total DNA methylation (5mC+5hmC), true DNA methylation (5mC) and hydroxymethylation (5hmC) levels were profiled utilizing conventional bisulphite (BS) and oxidative bisulphite (oxBS) treatment, measured with the Illumina Infinium Methylation EPIC BeadChip. An epigenome-wide association study (EWAS) of 5mC+5hmC methylation revealed a total of 38,575 differentially methylated positions (DMPs) and 2023 differentially methylated regions (DMRs) associated with current smoking, along with 82 DMPs and 76 DMRs associated with former smoking (FDR-adjusted < 0.
View Article and Find Full Text PDFBackground: Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans.
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- Restless legs syndrome (RLS) affects nearly 10% of older adults, but many face delays in diagnosis and treatment.
- A large-scale genetic study identified 164 risk loci for RLS, enhancing our understanding of its genetic basis and showing similarities in genetic predispositions between sexes.
- Findings suggest potential drug targets, a relationship between RLS and diabetes, and highlight the effectiveness of machine learning in predicting RLS risk using genetic and other data.
Background And Aims: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.
View Article and Find Full Text PDFAccurate risk prediction for myocardial infarction (MI) is crucial for preventive strategies, given its significant impact on global mortality and morbidity. Here, we propose a novel deep-learning approach to enhance the prediction of incident MI cases by incorporating metabolomics alongside clinical risk factors. We utilized data from the KORA cohort, including the baseline S4 and follow-up F4 studies, consisting of 1454 participants without prior history of MI.
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- Scientists studied how drinking alcohol affects our DNA and blood pressure.
- They found that for each drink a person consumes daily, blood pressure increases a bit and they are more likely to develop high blood pressure.
- However, over time, drinking habits didn't seem to change blood pressure levels, showing that tracking alcohol effects can help understand health.
Article Synopsis
- * The research showed that individuals with high polygenic risk scores have significantly higher blood pressure (almost 17 mmHg more) and over seven times the risk of developing hypertension compared to those with low scores.
- * Incorporating these genetic risk scores into hypertension prediction models improved their accuracy, and excitingly, similar genetic associations were found in a large African-American sample, underscoring the potential of these findings for precision health initiatives.
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- PCSK9 is important in lipid metabolism, with higher levels in women throughout their lives, and statin treatment influences these levels with potential genetic variances affecting results by sex.* -
- The study involved meta-analyses of PCSK9 levels in over 14,000 individuals, analyzing the effects of both sex and statin treatment on genetic associations related to PCSK9 and LDL cholesterol levels.* -
- Results highlighted 11 genetic loci linked to PCSK9, with some showing different effects based on sex and statin status, including novel associations for specific groups; this suggests distinct genetic influences on cholesterol levels based on gender and medication use.*
Article Synopsis
- Scientists studied how drinking alcohol affects our health by looking at changes in our DNA caused by alcohol, called DNA methylation.
- They created a special score to measure the effects of alcohol on people's health using data from nearly 4,000 people.
- They found that higher alcohol consumption was linked to increased blood pressure, but it didn't change over time or cause long-term issues with high blood pressure.
Article Synopsis
- - This study conducted a genome-wide association analysis on metabolic traits in over 136,000 participants, revealing over 400 genetic loci that influence human metabolism and complex diseases.
- - Researchers used advanced techniques like nuclear magnetic resonance spectroscopy to link specific genetic variants with how they affect lipoprotein metabolism and other metabolic processes.
- - The findings highlight the genetic connections between metabolism and conditions such as hypertension, providing valuable data for further research on metabolic-related diseases.
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- Type 2 diabetes (T2D) is a complex disease influenced by various genetic factors and molecular mechanisms that vary by cell type and ancestry.
- In a large study involving over 2.5 million individuals, researchers identified 1,289 significant genetic associations linked to T2D, including 145 new loci not previously reported.
- The study categorized T2D signals into eight distinct clusters based on their connections to cardiometabolic traits and showed that these genetic profiles are linked to vascular complications, emphasizing the role of obesity-related processes across different ancestry groups.
Background: Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS).
View Article and Find Full Text PDFBackground: The dicarbonyl compounds methylglyoxal (MG), glyoxal (GO) and 3-deoxyglucosone (3-DG) have been linked to various diseases. However, disease-independent phenotypic and genotypic association studies with phenome-wide and genome-wide reach, respectively, have not been provided.
Methods: MG, GO and 3-DG were measured by LC-MS in 1304 serum samples of two populations (KORA, n = 482; BiDirect, n = 822) and assessed for associations with genome-wide SNPs (GWAS) and with phenome-wide traits.
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- A genome-wide association study was conducted on thyroid function, analyzing data from up to 271,040 European individuals, focusing on hormones like TSH, FT4, and T3.
- The study identified 259 significant genetic associations for TSH (61% were novel), and notable findings for FT4 and T3, indicating that specific genes influence thyroid hormone levels and metabolism.
- The research findings enhance the understanding of thyroid hormone roles and suggest that variations in thyroid function may impact various health conditions including cardiovascular issues, autoimmune diseases, and cancer.