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373
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18,686
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Citations since 2017
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November 2012 - present
December 2010 - October 2012
July 2007 - June 2010
Publications
Publications (373)
Introduction: Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition.
Methods: In the present study, we defined quantitat...
Dysbiosis of the gut microbiome is a hallmark of inflammatory bowel disease (IBD) and both, IBD risk and microbiome composition, have been found to be associated with genetic variation. Using data from families of IBD patients, we examined the association between genetic and microbiome similarity in a specific IBD context, followed by a genome-wide...
Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome.'' Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairm...
The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors...
Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across t...
The Food Chain Plus (FoCus) cohort was launched in 2011 for population-based research related to metabolic inflammation. To characterize this novel pathology in a comprehensive manner, data collection included multiple omics layers such as phenomics, microbiomics, metabolomics, genomics, and metagenomics as well as nutrition profiling, taste percep...
Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT3Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrh...
(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in...
The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (...
Background:
Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PC...
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline r...
Scope:
The gut microbiome regulates various metabolic pathways in the host and its dysbiosis is involved in the pathogenesis of diverse diseases. Multiple factors modulate the composition of the microbiome and how it physiologically functions, but one of the major factors triggering gut microbiome establishment is diet. We aim to unravel interacti...
Purpose
Experimental evidence suggests positive effects of boron on health and metabolism, but human data are still scarce. We aimed to identify dietary and cardio-metabolic correlates of plasma boron concentrations in the general population.
Methods
In a community-based sample ( n = 899, 57% men, mean age 61 years), plasma boron (median [IQR]: 33...
Autoimmune neurological syndromes (AINS) with autoantibodies against the 65 kDa isoform of the glutamic acid decarboxylase (GAD65) present with limbic encephalitis including temporal lobe seizures or epilepsy, cerebellitis with ataxia, and stiff-person-syndrome, or overlap forms. Anti-GAD65 autoantibodies are also detected in autoimmune diabetes me...
Objective
One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls...
Background and Aims
Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn’s disease (CD) or ulcerative colitis (UC). These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations an...
Better drugs are needed for common epilepsies. Drug repurposing offers the potential of significant savings in the time and cost of developing new treatments. In order to select the best candidate drug(s) to repurpose for a disease, it is desirable to predict the relative clinical efficacy that drugs will have against the disease. Common epilepsy c...
Background
The association of longitudinal trajectories of cardiovascular risk factors with cardiovascular magnetic resonance (CMR)-measures of cardiac structure and function in the community is not well known. Therefore we aimed to relate risk factor levels from different examination cycles to CMR-measures of the left ventricle (LV) and right vent...
Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus ta...
Idiopathic Parkinson’s disease (PD) is a complex multifactorial disorder caused by the interplay of both genetic and non-genetic risk factors. Polygenic risk scores (PRSs) are one way to aggregate the effects of a large number of genetic variants upon the risk for a disease like PD in a single quantity. However, reassessment of the performance of a...
Background and Objectives
To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-NMDA receptor (anti-NMDAR) encephalitis.
Methods
We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls, followed by a colocalization analysis to id...
Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 5...
We assessed, for the first time, to what extent the composition of the gut microbiome might explain the cross-sectional association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure (BP) in a community-based sample (N=904) from Northern Germany. Gut microbiome composition was sequenced from 16S ribosoma...
Aims
Various studies reported that young European women are more likely to develop early-onset periodontitis compared with men. A potential explanation for the observed variations in sex and age-of-disease-onset is natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the inc...
Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense...
Background
Plant-rich diets are associated with lower cardiometabolic risks and longer survival in the general population, but their association with mortality in cancer survivors is still unclear.
Objectives
We aimed to examine the associations of 3 postdiagnostic plant-based diet indices with all-cause mortality in omnivorous long-term colorecta...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22613-2
Objective
Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.
Design
We conducted a GWAS meta-analysi...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced indivi...
Objective: To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis.
Methods: We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls followed by a colocalization analysis to id...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced indivi...
Objective
An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk fa...
To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide associa...
The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory1,2, neurologic³ and neoplastic diseases⁴. Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure r...
Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62,488 co...
Hemorrhoidal disease (HEM) affects a large fraction of the population but its etiology including suspected genetic predisposition is poorly understood. We conducted a GWAS meta-analysis of 218,920 HEM patients and 725,213 controls of European ancestry, demonstrating modest heritability and genetic correlation with several other diseases from the ga...
Background and Aims
To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in PSC compared to healthy controls (HCs) and inf...
Metabolomics can be a tool to identify dietary biomarkers. However, reported food-metabolite associations have been inconsistent, and there is a need to explore further associations. Our aims were to confirm previously reported food-metabolite associations and to identify novel food-metabolite associations. We conducted a cross-sectional analysis o...
Background:
Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by intracellular accumulations of α-synuclein and nerve cell loss in striatonigral and olivopontocerebellar structures. Epidemiological and clinical studies have reported potential involvement of autoimmune mechanisms in MSA pathogenesis. However, genetic e...
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases...
Objective
Genetic risk factors for unruptured intracranial aneurysms (UIA) and aneurysmal subarachnoid hemorrhage (aSAH) are poorly understood. We aimed to verify recently reported risk genes and to identify novel sequence variants involved in the etiology of UIA/aSAH.Methods
We performed exome sequencing (ES) in 35 unrelated individuals and 3 fami...
Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a...
Objectives
To assess the prevalence and severity of perirenal hyperintensities (PRHs) on T2-weighted magnetic resonance imaging (MRI) and their risk factors in the general population.Methods1752 participants (910 women, 842 men, median age: 52 years) of the Study of Health in Pomerania were included. A visual classification system was established t...
Background
Although lifestyle modifications are an integral part of treatment and prevention of hemorrhoidal disease, it is largely unknown how lifestyle factors like diet and physical activity are characterized in patients with a history of advanced and invasively treated hemorrhoidal disease.Methods
In a Northern German cross-sectional study, cli...
The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory neurologic and neoplastic diseases. Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains...
Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of...
To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed whole-genome genotypes and 16S fecal microbiome data from 18,473 individuals (25 cohorts). Microbial composition showed high variability across cohorts: we detected only 9 out of 410 genera in more than 95% of the samples. A genome-wide...
We describe a novel dietary assessment strategy to estimate usual food intake in the ongoing large-scale multi-center German National Cohort (GNC). The dietary assessment is based on three 24 h food lists (24h-FL) and a food frequency questionnaire (FFQ) enriched by information from the representative German National Nutrition Survey II (NVS II). T...
Purpose
The aim of the present study was to derive overall and sex-specific dietary patterns associated with inflammatory biomarkers in a general population sample from Northern Germany.
Methods
The present analysis included 1158 participants (477 men, 681 women, mean age: 53.1 years; mean body mass index: 26.2 kg/m²) of the Food Chain Plus (FoCus...
Background
The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH.
Aim
To investigate disease‐specific microbiome alterations in AIH.
Methods
The V1‐V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy...
Background: Better adherence to plant-based diets has been linked to lower risk of metabolic diseases but the effect on abdominal fat distribution and liver fat content is unclear.
Objectives: We aimed to examine the association between different plant-based diet indices and measures of abdominal fat distribution and liver fat content.
Methods: I...
Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk fa...
Objective:
Impaired lysosomal degradation of α-synuclein and other cellular constituents may play an important role in Parkinson's disease (PD). Rare genetic variants in the glucocerebrosidase (GBA) gene were consistently associated with PD. Here we examine the association between rare variants in lysosomal candidate genes and PD.
Methods:
We in...
Background
Musculoskeletal diseases and symptoms are very common in the general population. They lead to high healthcare costs and pose a significant burden to the national economy.Objectives
Based on data from the population-based German National Cohort (GNC), frequencies of musculoskeletal symptoms and diseases are reported, including back pain,...
Background: Infectious diseases continue to play an important role for disease perception, healtheconomic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pav...
Background
In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants.Objectives
Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first result...