Stefan Stender

Stefan Stender
Rigshospitalet | rigshospitalet · Department of Clinical Biochemistry

MD, PhD

About

54
Publications
8,036
Reads
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3,544
Citations
Additional affiliations
September 2004 - August 2005
National University of Ireland, Galway
Position
  • Researcher (undergraduate)
Education
September 2000 - June 2007
Århus University
Field of study
  • Medicine

Publications

Publications (54)
Article
Full-text available
The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a p...
Article
Background: A genetic variant in the manganese transporter SLC30A10 (rs188273166, p.Thr95Ile) was associated with increased plasma alanine transaminase (ALT) in a recent genome-wide association study in the UK Biobank (UKB). The aims of the present study were to test the association of rs188273166 with ALT in an independent cohort, and to begin to...
Preprint
Full-text available
Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP,...
Article
Full-text available
Background and aims Individual risk for developing alcohol-related liver disease (ALD) varies greatly. We hypothesized that metabolic risk factors and genetic polymorphisms predict severity of ALD. Methods Biopsy-controlled, cross-sectional study in patients with a history of excessive drinking. We measured the homeostatic model assessment of insu...
Article
Full-text available
Background & Aims A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of N...
Article
Background: People living with HIV (PWH) may be at risk of non-alcoholic fatty liver disease (NAFLD). We compared the prevalence of moderate-to-severe hepatic steatosis (M-HS) in PWH with HIV-uninfected controls and determined risk factors for M-HS in PWH. Methods: The Copenhagen Co-Morbidity in HIV infection Study included 453 participants and...
Article
Full-text available
Context A common genetic variant near PPP1R3B (rs4841132G>A) has been associated with increased hepatic computed tomography (CT) attenuation, and with plasma levels of glucose and liver enzymes. Objective To elucidate the association of rs4841132 with hepatic CT attenuation, and to test if synergistic effects modify the association of the variant...
Article
Full-text available
Background and aims: We hypothesized that a genetic risk score (GRS) for fatty liver disease influences the risk of cirrhosis and hepatocellular carcinoma (HCC). Three genetic variants (patatin-like phospholipase domain-containing protein 3 [PNPLA3] p.I148M; transmembrane 6, superfamily member 2 [TM6SF2] p.E167K; and hydroxysteroid 17-beta dehydro...
Article
Mirroring the obesity pandemic, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease affecting populations worldwide. Approximately 30% of the adult United States (US) population is estimated to be afflicted with NAFLD. NAFLD is a spectrum of liver disease ranging from nonalcoholic fatty liver (NAFL), the non‐progressiv...
Article
Full-text available
Carbon‐13 magnetic resonance spectroscopy (MRS) following oral intake of 13C‐labeled glucose is the gold standard for imaging glycogen metabolism in humans. However, the temporal resolution of previous studies has been >13 minutes. Here, we describe a high‐sensitivity 13C MRS method for imaging hepatic glycogen synthesis with a temporal resolution...
Preprint
Full-text available
Background & Aims A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of N...
Article
Full-text available
Background Elevated plasma concentrations of liver enzymes are routinely used as markers of liver injury in adults and children. Currently, the age- and sex-specific effects of adiposity on pediatric liver enzyme concentrations are unclear. Methods We included participants from two cohorts of Danish children and adolescents: 1,858 from a populatio...
Article
A common loss‐of‐function variant in HSD17B13 (rs72613567:TA) was recently found to protect from chronic liver disease. Whether the variant confers protection from specific risk factors for liver disease is unclear. We tested the association of rs72613567 with plasma levels of alanine transaminase (ALT) and clinical liver disease and mortality in 1...
Chapter
Full-text available
Non-alcoholic fatty liver disease (NAFLD) is a buildup of excessive fat in the liver that can lead to liver damage resembling the damage caused by alcohol abuse, but that occurs in people who do not drink heavily. The disease is of complex and of multifactorial origin. Insulin resistance and obesity are considered major risk factors for the develop...
Article
Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify new genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts. We extracted genetic...
Data
Data S1. Supplementary methods. Data S2. Supplementary results. Table S1. Noninvasive fibrosis scores tested in the DHS for association with hepatic fat content. Table S2. Coefficient used to develop genetic risk scores (GRS) applied in the study cohorts (full models and sensitivity analysis conducted by removing one genetic variant at time). T...
Article
Background Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. Methods We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate...
Article
Full-text available
Background and aims: Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. Methods: We performed a Mendelian randomization analysis using risk alleles in PNPL...
Article
Genetic variation at rs4240624 on chromosome 8 is associated with an attenuated signal on hepatic computerized tomography, which has been attributed to changes in hepatic fat. The closest coding gene to rs4240624, PPP1R3B, encodes a protein that promotes hepatic glycogen synthesis. Here, we performed studies to determine whether the x-ray attenuati...
Article
Aims: In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results: In a cohort study of the Danish general population (n = 94 708/IHD = 10 897),...
Article
Background: Results from randomized controlled trials (RCTs) have raised concern that the cholesterol-lowering drug ezetimibe might increase the risk of cancer. We tested the hypothesis that genetic variation in NPC1L1 , mimicking treatment with ezetimibe, was associated with an increased risk of cancer. Methods: We included 67 257 individuals f...
Article
Complex traits arise from the interplay between genetic and environmental factors. The actions of these factors usually appear to be additive, and few compelling examples of gene-environment synergy have been documented. Here we show that adiposity significantly amplifies the effect of three sequence variants (encoding PNPLA3 p.I148M, TM6SF2 p.E167...
Article
Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7,...
Article
Purpose of review: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. Recent findings: LDL cholesterol lowering variants in HMG-Coenzyme A reductase and Niemann-Pick C1-like protein 1, the ta...
Article
Full-text available
Ezetimibe reduces plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting Niemann-Pick C1-Like protein 1 (NPC1L1), the transporter responsible for cholesterol uptake from the intestine into enterocytes and from the bile into hepatocytes. We tested the hypothesis that genetic variation in NPC1L1, mimicking the effect of ezetimibe, w...
Article
Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916...
Article
Two new studies report that triglyceride (TG)-lowering mutations in APOC3 reduce coronary heart disease (CHD) (Crosby et al., 2014; Jørgensen et al., 2014). Here, we explore limitations of using Mendelian randomization to evaluate CHD risk, including potential confounding by the widespread use of statin therapy.
Article
Objective To test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, might simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction(MI) and gallstone disease in opposite directions. Background High plasma levels of low-den...
Article
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease. To elucidate the molecular basis of NAFLD, we performed an exome-wide association study of liver fat content. Three variants were associated with higher liver fat levels at the exome-wide significance level of 3.6 × 10(-7): two in PNPLA3, an established locus for NAF...
Article
Unlabelled: Elevated body mass index (BMI) is associated with an increased risk of gallstone disease. Whether this reflects a causal association is unknown. Using a Mendelian randomization approach, we studied 77,679 individuals from the general population. Of these, 4,106 developed symptomatic gallstone disease during up to 34 years of follow-up....
Article
Full-text available
Importance: In individuals without blockage of their bile ducts, levels of plasma bilirubin likely reflect levels of biliary bilirubin; higher biliary bilirubin levels may increase the risk of gallstone disease. Objective: To test the hypothesis that a lifelong increase in plasma bilirubin levels is a causal risk factor for symptomatic gallstone...
Article
Background & aims: Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone disease. Methods: We used a Mendeli...
Data
UCSC Genome Browser Chromatin Annotations for Variants in Complete LD with rs7120118. The map shows the location of 8 SNPs in complete LD with rs7120118. Lymphoblast open chromatin and H3K4me1 marks derived from the UCSC Genome Browser are annotated. The regions of distinct enhancers are highlighted in red, illustrating the location of SNPs in comp...
Data
Lymphobast cell lines used for FAIRE-gen. The cell lines used for the CVD BeadChip and the Metabochip study are indicated. (DOCX)
Data
Histogram of FAIRE-gen p-values for 50K CVD BeadChip. The use of FAIRE-gen on the CVD BeadChip was carried out with a very small number of samples, resulting in only one SNP showing chip-wide significance in relation to chromatin structure. The enrichment of p-values<0.05, indicates the potential for a greater level of functionality to be derived f...
Article
Full-text available
Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAI...
Article
Background: Elevated plasma levels of bilirubin, an endogenous antioxidant, have been associated with reduced risk of ischaemic heart disease (IHD) and myocardial infarction (MI). Whether this is a causal relationship remains unclear. Objective: We tested the hypothesis that elevated plasma bilirubin is causally related to decreased risk of IHD...
Article
Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population. We studied 10,281 white persons of...
Article
Unlabelled: Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer in the general population, we studied 62...
Article
Full-text available
Low plasma levels of low-density lipoprotein (LDL) cholesterol are associated with an increased risk of cancer, but whether this association is causal is unclear. We studied 10 613 participants in the Copenhagen City Heart Study (CCHS) and 59 566 participants in the Copenhagen General Population Study, 6816 of whom had developed cancer by May 2009....
Article
Full-text available
Mesenchymal stem cells (MSCs) have received considerable attention in the emerging field of regenerative medicine. One aspect of MSC research focuses on genetically modifying the cells with the aim of enhancing their regenerative potential. Adeno-associated virus (AAV) holds promise as a vector for human gene therapy, primarily due to its lack of p...

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