Publications by authors named "Volker Koenig"

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.

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  • The study investigates the genetic factors contributing to the decline in estimated glomerular filtration rate (eGFR), a key indicator of kidney function, by analyzing data from 62 longitudinal studies involving over 343,000 participants.
  • Twelve significant genetic variants related to eGFR decline were identified, with most showing interaction effects based on age, which highlights how genetic influences on kidney function change as individuals get older.
  • The findings emphasize that individuals with certain genetic profiles face higher risks for kidney failure and acute kidney injury, providing valuable insights that could aid in drug development and strategies for managing kidney health.
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  • Reduced glomerular filtration rate (GFR) is a precursor to kidney failure, influenced by factors like genetics and diabetes (DM), but the interaction between these factors is not well understood.
  • A large-scale genome-wide association study (GWAS) analyzed eGFR across almost 1.5 million individuals, revealing distinct genetic loci that differ between those with and without diabetes.
  • The findings identified potential new targets for drug development aimed at protecting kidney function, highlighting that many drug interventions could be effective for both diabetic and non-diabetic populations.
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  • * The study identified 100 significant CpG sites that account for 11.6% of serum urate variance, particularly noting five CpGs associated with SLC2A9, a major gene influencing serum urate levels.
  • * Additionally, some of these CpGs also appear to mediate effects of genetic variants related to serum urate and are linked to metabolic syndrome, suggesting a potential blood DNA methylation signature for assessing cardiometabolic risk factors.
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Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry.

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  • - The study investigates the genetic factors contributing to the rapid decline in glomerular filtration rate (eGFRcrea), using data from 42 genome-wide association studies to analyze genetic loci linked to this decline.
  • - Two specific definitions of rapid eGFRcrea decline are examined, leading to the identification of seven independent genetic variants associated with this condition, including significant findings near three novel loci.
  • - The research suggests that individuals with a higher genetic risk for kidney function decline are more likely to experience acute kidney injury, indicating that these identified genetic loci could help in developing targeted therapies and identifying at-risk individuals.
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Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy.

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  • Increased urinary albumin-to-creatinine ratio (UACR) is linked to higher risks of kidney disease and cardiovascular issues, yet the underlying causes are not fully understood.
  • A large meta-analysis identified 68 genetic loci associated with UACR, highlighting connections to conditions like proteinuria, hyperlipidemia, and hypertension.
  • Specific genes (such as TGFB1 and PRKCI) were implicated in kidney function, and experiments showed that disrupting these genes in fruit flies affects albumin processing, suggesting new avenues for research to lower albumin levels.
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Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178).

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  • The article with DOI 10.1371/journal.pgen.1005378 has been revised to correct previous errors.
  • The corrections enhance the accuracy and clarity of the findings presented.
  • Researchers and readers are encouraged to refer to the updated version for the most reliable information.
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Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci.

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Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.

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Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels.

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Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium.

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Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.

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  • Obesity has a genetic component and is linked to various diseases, prompting a large-scale study involving over 339,000 participants to explore its genetic basis through BMI analysis.
  • The study identified 97 loci associated with BMI, with 56 being new discoveries, and found that these loci explain about 2.7% of the variation in BMI, while common genetic variations contribute over 20%.
  • Results indicate that the central nervous system plays a significant role in obesity risk and point to new genes and pathways related to brain function, metabolism, and fat development.
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Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)).

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In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity.

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Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population.

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In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations.

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Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80.

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Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria.

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Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m(2); n = 5,807 individuals with CKD (cases)).

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