Markus Löffler

About Markus Löffler:

Prof. Dr. Markus Löffler Universität Leipzig Institut für Medizinische Informatik, Statistik und Epidemiologie Härtelstraße 16-18 04107 Leipzig

LHA ID: 7W2GKE4JDQ-2

Location:  Germany

ORCID: Not specified

Expertise: Not specified

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Project positions

Genetical Statistics and Systems Biology (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; LIFE HNC - Head and Neck Cancer Group (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; MMML-MYC-SYS (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; LIFE Adult (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; GLA - German Lymphoma Alliance (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; MMML - Molecular mechanisms in malignant lymphoma (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; SepNet - German Competence Network Sepsis (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; SMITH - Smart Medical Information Technology for Healthcare (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; LHA - Leipzig Health Atlas (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; POLAR - Polypharmacy, Drug Interactions, Risks (Institute for Medical Informatics, Statistics and Epidemiology (IMISE)) ; SMITH - Smart Medical Information Technology for Healthcare (University of Leipzig) ; Task Force COVID-19 Leipzig (Institute for Medical Informatics, Statistics and Epidemiology (IMISE))

Related items

LIFE HNC - Head and Neck Cancer Group

The aim of the Head and Neck Group within the Leipzig Research Center for Civilization Diseases (LIFE) is to facilitate improvements in the treatment and care of head and neck cancer patients through insights from molecular studies.

The Head and Neck Group within the Leipzig Research Center for Civilization Diseases (LIFE) investigates the molecular mechanisms and the diagnostic and prognostic factors of head and neck cancer. For this purpose, we collected phenotypic information from about 300 ...

Programme: This Project is not associated with a Programme

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2012

End date: 31st Dec 2012

LIFE - Leipzig Research Center for Civilization Diseases: inactive since

Goal of the Leipzig Research Center for Civilization Diseases (LIFE) is the investigation of civilization diseases like depression, diabetes, allergies or cardiovascular diseases. For this purpose we collect as much data as possible regarding health and living conditions of the population in Leipzig and provide these data for scientists of the University of Leipzig and other research institutions.

Programme: Epidemiology

Public web page: http://life.uni-leipzig.de/

Start date: 1st Jan 2009

LIFE Adult

This population-based study examined 10,000 participants randomly selected from the Leipzig population (2011 to 2014). A follow-up is to be carried out from 2017 - 2020. The study mainly included people aged between 40 and 79. All participants underwent a 6-hour study program and people over 60 years of age were invited two more times to in-depth study of cognition and depression and the brain (MRI, EEG). Extensive measurements of genome, metabolome and transcriptome are available. The LIFE-ADULT ...

Programme: Epidemiology

Public web page: http://life.uni-leipzig.de/en/adults/life_adult.html

Start date: 1st Jan 2009

Task Force COVID-19 Leipzig

This project serves as a container for all COVID-19 related assets, developed at the University of Leipzig and its partners.

Programme: NFDI4Health

Public web page: https://www.nfdi4health.de/task-force-covid-19

Start date: 20th May 2020

SMITH - Smart Medical Information Technology for Healthcare
No description specified

Programme: MII - Medical Informatics Initiative

Public web page: https://www.smith.care/

Start date: 1st Jan 2018

LHA - Leipzig Health Atlas

The Leipzig Health Atlas (LHA) is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields in which our team has scientific and clinical expertise.

Programme: This Project is not associated with a Programme

Public web page: https://www.health-atlas.de

Start date: 1st Apr 2016

End date: 28th Feb 2021

MMML - Molecular mechanisms in malignant lymphoma

During 2003 and 2011 the german cancer aid funded the molecular mechanisms in malignant lymphomas (MMML) project. It is based on strongly interacting networks of reference pathologists, lymphoma scientists, bioinformaticians and clinical trial groups. Within the project about 1000 lymphoma samples and controls were characterized by gene expression and copy number arrays. The datasets were supplemented by extensive histopathological and clinical descriptions of the lymphoma cases. The aim of the ...

Programme: This Project is not associated with a Programme

Public web page: Not specified

MMML-MYC-SYS

MMML-MYC-SYS is a interdisciplinary consortium where partners from clinical haemaoncological study groups, pathologists, geneticicts, cell biologists as well as mathematicians, statisticians and bioinformaticists have allied. The goal is to investigate the process of development of B-cell lymphoma under special consideration of mutation of MYC. MYC is known to support the development and growth of tumors. This consortium collected and evaluated comprehensive molecular-genetic data for this purpose. ...

Programme: This Project is not associated with a Programme

Public web page: http://www.mmmlmycsys.de/

Start date: 1st Jan 2013

MMML Demonstrators - Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine

The joint project "MMML Demonstrators" deals with improvements in the diagnosis and therapy of lymphoma and consists of seven subprojects. In lymphoma, the so-called diffuse large cell B-cell lymphomas (DLBCL) are responsible for the highest number of deaths. Although the disease is curable in principle, approximately one third of patients still die. However, the expression of certain genes in tumor cells and surrounding tissues can be used to diagnose certain subgroups of these tumors and, in ...

Programme: This Project is not associated with a Programme

Public web page: https://www.sys-med.de/de/demonstratoren/mmml-demonstrators/

Start date: 1st Jan 2015

End date: 31st Dec 2018

SepNet - German Competence Network Sepsis

As an interdisciplinary network of scientists, the SepNet study group deals with the topics of severe sepsis and septic shock. The aim of the network is to create the prerequisites for better clinical and experimental research into sepsis and thus to develop efficient treatment approaches.

Programme: Epidemiology

Public web page: https://www.sepsis-stiftung.eu/sepnet/

Start date: 1st Jan 2003

Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP Trial)
SepNet - German Competence Network Sepsis

Severe sepsis and septic shock have a high mortality. Research has concentrated on adjunctive sepsis therapies; the role of supportive measures is comparatively unclear. In Europe the use of colloids is widespread, but there is no evidence on the role of either crystalloid or colloid volume therapy in sepsis. Recently, a higher incidence of kidney failure in sepsis was reported after administration of colloids.

Submitter: Christoph Beger

Studies: VISEP

Resources: VISEP metadata, VISEP trial data

VISEP
SepNet - German Competence Network Sepsis

Baseline Data and Endpoints for VISEP

Submitter: René Hänsel

Investigation: Efficacy of Volume Substitution and Insulin The...

Resources: VISEP metadata, VISEP trial data

Study type: Not specified

VISEP trial data
SepNet - German Competence Network Sepsis

The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. We compared intensive insulin therapy with conventional insulin therapy and HES with Ringer’s lactate.

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: Efficacy of Volume Substitution and Insulin The...

Study: VISEP

VISEP metadata
SepNet - German Competence Network Sepsis

The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. We compared intensive insulin therapy with conventional insulin therapy and HES with Ringer’s lactate.

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Investigation: Efficacy of Volume Substitution and Insulin The...

Study: VISEP

The Human Blood Transcriptome in a Large Population Cohort and Its Relation to Aging and Health.
LIFE Adult, oBIG - omics Bioinformatics for Health

Abstract (Expand)

Background: The blood transcriptome is expected to provide a detailed picture of an organism's physiological state with potential outcomes for applications in medical diagnostics and molecular and … epidemiological research. We here present the analysis of blood specimens of 3,388 adult individuals, together with phenotype characteristics such as disease history, medication status, lifestyle factors, and body mass index (BMI). The size and heterogeneity of this data challenges analytics in terms of dimension reduction, knowledge mining, feature extraction, and data integration. Methods: Self-organizing maps (SOM)-machine learning was applied to study transcriptional states on a population-wide scale. This method permits a detailed description and visualization of the molecular heterogeneity of transcriptomes and of their association with different phenotypic features. Results: The diversity of transcriptomes is described by personalized SOM-portraits, which specify the samples in terms of modules of co-expressed genes of different functional context. We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. We find a striking overlap of signatures shared by multiple diseases, aging, and obesity driven by an underlying common pattern, which was associated with the immune response and the increase of inflammatory processes. Conclusions: Machine learning applications for large and heterogeneous omics data provide a holistic view on the diversity of the human blood transcriptome. It provides a tool for comparative analyses of transcriptional signatures and of associated phenotypes in population studies and medical applications.

Authors: M. Schmidt, L. Hopp, A. Arakelyan, H. Kirsten, C. Engel, K. Wirkner, K. Krohn, R. Burkhardt, J. Thiery, M. Loeffler, H. Loeffler-Wirth, H. Binder

Date Published: 11th Mar 2021

Publication Type: Journal article

Dynamics of cytokines, immune cell counts and disease severity in patients with community-acquired pneumonia - Unravelling potential causal relationships
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Community acquired pneumonia (CAP) is a severe and often rapidly deteriorating disease. To better understand its dynamics and potential causal relationships, we analyzed time series data of …f cytokines, blood and clinical parameters in hospitalized CAP patients. METHODS Time series data of 10 circulating cytokines, blood counts and clinical parameters were related to baseline characteristics of 403 CAP patients using univariate mixed models. Bivariate mixed models were applied to analyze correlations between the time series. To identify potential causal relationships, we inferred cross-lagged relationships between pairs of parameters using latent curve models with structured residuals. RESULTS IL-6 levels decreased faster over time in younger patients (Padj = 0.06). IL-8, VCAM-1, and IL-6 correlated strongly with disease severity as assessed by the sequential organ failure assessment (SOFA) score (r = 0.49, 0.48, 0.46, respectively; all Padj \textless 0.001). IL-6 and bilirubin correlated with respect to their mean levels and slopes over time (r = 0.36 and r = 0.46, respectively; Padj \textless 0.001). A number of potential causal relationships were identified, e.g., a negative effect of ICAM-1 on MCP-1, or a positive effect of the level of creatinine on the subsequent VCAM-1 concentration (P \textless 0.001). CONCLUSIONS These results suggest that IL-6 trajectories of CAP patients are associated with age and run parallel to bilirubin levels. The time series analysis also unraveled directed, potentially causal relationships between cytokines, blood parameters and clinical outcomes. This will facilitate the development of mechanistic models of CAP, and with it, improvements in treatment or surveillance strategies for this disease. TRIAL REGISTRATION clinicaltrials.gov NCT02782013, May 25, 2016, retrospectively registered.

Authors: Maciej Rosolowski, Volker Oberle, Peter Ahnert, Petra Creutz, Martin Witzenrath, Michael Kiehntopf, Markus Loeffler, Norbert Suttorp, Markus Scholz

Date Published: 1st Dec 2020

Publication Type: Journal article

Integration of mathematical model predictions into routine workflows to support clinical decision making in haematology
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Individualization and patient-specific optimization of treatment is a major goal of modern health care. One way to achieve this goal is the application of high-resolution diagnostics together …r with the application of targeted therapies. However, the rising number of different treatment modalities also induces new challenges: Whereas randomized clinical trials focus on proving average treatment effects in specific groups of patients, direct conclusions at the individual patient level are problematic. Thus, the identification of the best patient-specific treatment options remains an open question. Systems medicine, specifically mechanistic mathematical models, can substantially support individual treatment optimization. In addition to providing a better general understanding of disease mechanisms and treatment effects, these models allow for an identification of patient-specific parameterizations and, therefore, provide individualized predictions for the effect of different treatment modalities. RESULTS In the following we describe a software framework that facilitates the integration of mathematical models and computer simulations into routine clinical processes to support decision-making. This is achieved by combining standard data management and data exploration tools, with the generation and visualization of mathematical model predictions for treatment options at an individual patient level. CONCLUSIONS By integrating model results in an audit trail compatible manner into established clinical workflows, our framework has the potential to foster the use of systems-medical approaches in clinical practice. We illustrate the framework application by two use cases from the field of haematological oncology.

Authors: Katja Hoffmann, Katja Cazemier, Christoph Baldow, Silvio Schuster, Yuri Kheifetz, Sibylle Schirm, Matthias Horn, Thomas Ernst, Constanze Volgmann, Christian Thiede, Andreas Hochhaus, Martin Bornhäuser, Meinolf Suttorp, Markus Scholz, Ingmar Glauche, Markus Loeffler, Ingo Roeder

Date Published: 1st Dec 2020

Publication Type: Journal article

Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, … such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. METHODS: We analyzed 347 participants (age range: 20-59 years, BMI range: 17-38 kg/m(2)) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. RESULTS: Higher BMI was significantly associated with lower connectivity strength for number of streamlines (beta = -0.0025, 95%-C.I.: [-0.004, -0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (beta = -0.0009, 95%-C.I. [-0.0016, -0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. CONCLUSIONS: Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.

Authors: F. Beyer, R. Zhang, M. Scholz, K. Wirkner, M. Loeffler, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 25th Oct 2020

Publication Type: Journal article

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.
Genetical Statistics and Systems Biology

Abstract (Expand)

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide … associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/beta-catenin, TGF-beta and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

Authors: E. Hofer, G. V. Roshchupkin, H. H. H. Adams, M. J. Knol, H. Lin, S. Li, H. Zare, S. Ahmad, N. J. Armstrong, C. L. Satizabal, M. Bernard, J. C. Bis, N. A. Gillespie, M. Luciano, A. Mishra, M. Scholz, A. Teumer, R. Xia, X. Jian, T. H. Mosley, Y. Saba, L. Pirpamer, S. Seiler, J. T. Becker, O. Carmichael, J. I. Rotter, B. M. Psaty, O. L. Lopez, N. Amin, S. J. van der Lee, Q. Yang, J. J. Himali, P. Maillard, A. S. Beiser, C. DeCarli, S. Karama, L. Lewis, M. Harris, M. E. Bastin, I. J. Deary, A. Veronica Witte, F. Beyer, M. Loeffler, K. A. Mather, P. R. Schofield, A. Thalamuthu, J. B. Kwok, M. J. Wright, D. Ames, J. Trollor, J. Jiang, H. Brodaty, W. Wen, M. W. Vernooij, A. Hofman, A. G. Uitterlinden, W. J. Niessen, K. Wittfeld, R. Bulow, U. Volker, Z. Pausova, G. Bruce Pike, S. Maingault, F. Crivello, C. Tzourio, P. Amouyel, B. Mazoyer, M. C. Neale, C. E. Franz, M. J. Lyons, M. S. Panizzon, O. A. Andreassen, A. M. Dale, M. Logue, K. L. Grasby, N. Jahanshad, J. N. Painter, L. Colodro-Conde, J. Bralten, D. P. Hibar, P. A. Lind, F. Pizzagalli, J. L. Stein, P. M. Thompson, S. E. Medland, P. S. Sachdev, W. S. Kremen, J. M. Wardlaw, A. Villringer, C. M. van Duijn, H. J. Grabe, W. T. Jr Longstreth, M. Fornage, T. Paus, S. Debette, M. Arfan Ikram, H. Schmidt, R. Schmidt, S. Seshadri

Date Published: 22nd Sep 2020

Publication Type: Journal article

Pro-Neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-Neurotensin (NT) was associated with metabolic diseases …s and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far. METHODS In a central lab, circulating Pro-NT was quantified in three independent cohorts comprising 4,715 participants (cohort 1: patients with CKD; cohort 2: general population study; cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. Serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice. RESULTS Pro-NT significantly increased with deteriorating renal function (p\textless0.001). In meta-analysis of cohorts 1-3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (p\leq0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, p=0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals. CONCLUSIONS Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4,715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

Authors: Anke Toenjes, Annett Hoffmann, Susan Kralisch, Abdul Rashid Qureshi, Nora Klöting, Markus Scholz, Dorit Schleinitz, Anette Bachmann, Juergen Kratzsch, Marcin Nowicki, Sabine Paeschke, Kerstin Wirkner, Cornelia Enzenbach, Ronny Baber, Joachim Beige, Matthias Anders, Ingolf Bast, Matthias Blüher, Peter Kovacs, Markus Löffler, Ming-Zhi Zhang, Raymond C. Harris, Peter Stenvinkel, Michael Stumvoll, Mathias Fasshauer, Thomas Ebert

Date Published: 1st Sep 2020

Publication Type: Journal article

Genome-wide association analysis of pulse wave velocity traits provide new insights into the causal relationship between arterial stiffness and blood pressure
LIFE Adult

Abstract (Expand)

Background The pathophysiology of arterial stiffness is not completely understood. Pulse wave velocity (PWV) is an established marker for arterial stiffness. We compare genetics of three PWV modes, … namely carotid-femoral PWV (cfPWV), brachial-ankle (baPWV) and brachial-femoral (bfPWV), reflecting different vascular segments to analyse association with genetic variants, heritability and genetic correlation with other biological traits. Furthermore we searched for shared genetic architecture concerning PWV, blood pressure (BP) and coronary artery disease (CAD) and examined the causal relationship between PWV and BP. Methods and results We performed a genome-wide association study (GWAS) for cfPWV, baPWV and bfPWV in LIFE-Adult (N = 3,643–6,734). We analysed the overlap of detected genetic loci with those of BP and CAD and performed genetic correlation analyses. By bidirectional Mendelian Randomization, we assessed the causal relationships between PWV and BP. For cfPWV we identified a new locus with genome-wide significance near SLC4A7 on cytoband 3p24.1 (lead SNP rs939834: p = 2.05x10-8). We replicated a known PWV locus on cytoband 14q32.2 near RP11-61O1.1 (lead SNPs: rs17773233, p = 1.38x10-4; rs1381289, p = 1.91x10-4) For baPWV we estimated a heritability of 28% and significant genetic correlation with hypertension (rg = 0.27, p = 6.65x10-8). We showed a positive causal effect of systolic blood pressure on PWV modes (cfPWV: p = 1.51x10-4; bfPWV: p = 1.45x10-3; baPWV: p = 6.82x10-15). Conclusions We identified a new locus for arterial stiffness and successfully replicated an earlier proposed locus. PWV shares common genetic architecture with BP and CAD. BP causally affects PWV. Larger studies are required to further unravel the genetic determinants and effects of PWV.

Authors: Michael Rode, Andrej Teren, Kerstin Wirkner, Katrin Horn, Holger Kirsten, Markus Loeffler, Markus Scholz, Janne Pott

Date Published: 13th Aug 2020

Publication Type: Journal article

Human Diseases: arteriosclerosis, arteriosclerotic cardiovascular disease

Norms of Interocular Circumpapillary Retinal Nerve Fiber Layer Thickness Differences at 768 Retinal Locations
LIFE Adult

Abstract (Expand)

Purpose: The onset and progression of optic neuropathies like glaucoma often occurs asymmetrically between the two eyes of a patient. Interocular circumpapillary retinal nerve fiber layer thickness … (cpRNFLT) differences could detect disease earlier. To apply such differences diagnostically, detailed location specific norms are necessary. Methods: Spectral-domain optical coherence tomography cpRNFLT circle scans from the population-based Leipzig Research Centre for Civilization Diseases–Adult study were selected. At each of the 768 radial scanning locations, normative interocular cpRNFLT difference distributions were calculated based on age and interocular radius difference. Results: A total of 8966 cpRNFLT scans of healthy eyes (4483 patients; 55% female; age range, 20–79 years) were selected. Global cpRNFLT average was 1.53 µm thicker in right eyes (P < 2.2 × 10–16). On 96% of the 768 locations, left minus right eye differences were significant (P < 0.05), varying between +11.6 µm (superonasal location) and −11.8 µm (nasal location). Increased age and difference in interocular scanning radii were associated with an increased mean and variance of interocular cpRNFLT difference at most retinal locations, apart from the area temporal to the inferior RNF bundle where cpRNFLT becomes more similar between eyes with age. Conclusions: We provide pointwise normative distributions of interocular cpRNFLT differences at an unprecedentedly high spatial resolution of 768 A-scans and reveal considerable location specific asymmetries as well as their associations with age and scanning radius differences between eyes. Translational Relevance: To facilitate clinical application, we implement these age- and radius-specific norms across all 768 locations in an open-source software to generate patient-specific normative color plots.

Authors: Neda Baniasadi, Franziska G. Rauscher, Dian Li, Mengyu Wang, Eun Young Choi, Hui Wang, Thomas Peschel, Kerstin Wirkner, Toralf Kirsten, Joachim Thiery, Christoph Engel, Markus Loeffler, Tobias Elze

Date Published: 3rd Aug 2020

Publication Type: Journal article

Global and Regional Development of the Human Cerebral Cortex: Molecular Architecture and Occupational Aptitudes.
Genetical Statistics and Systems Biology

Abstract (Expand)

We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their … surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one’s occupation.

Authors: Jean Shin, Shaojie Ma, Edith Hofer, Yash Patel, Daniel E. Vosberg, Steven Tilley, Gennady V. Roshchupkin, André M. M. Sousa, Xueqiu Jian, Rebecca Gottesman, Thomas H. Mosley, Myriam Fornage, Yasaman Saba, Lukas Pirpamer, Reinhold Schmidt, Helena Schmidt, Amaia Carrion-Castillo, Fabrice Crivello, Bernard Mazoyer, Joshua C. Bis, Shuo Li, Qiong Yang, Michelle Luciano, Sherif Karama, Lindsay Lewis, Mark E. Bastin, Mathew A. Harris, Joanna M. Wardlaw, Ian E. Deary, Markus Scholz, Markus Loeffler, A. Veronica Witte, Frauke Beyer, Arno Villringer, Nicola J. Armstrong, Karen A. Mather, David Ames, Jiyang Jiang, John B. Kwok, Peter R. Schofield, Anbupalam Thalamuthu, Julian N. Trollor, Margaret J. Wright, Henry Brodaty, Wei Wen, Perminder S. Sachdev, Natalie Terzikhan, Tavia E. Evans, Hieab H. H. H. Adams, M. Arfan Ikram, Stefan Frenzel, Sandra van der Auwera-Palitschka, Katharina Wittfeld, Robin Bülow, Hans Jörgen Grabe, Christophe Tzourio, Aniket Mishra, Sophie Maingault, Stephanie Debette, Nathan A. Gillespie, Carol E. Franz, William S. Kremen, Linda Ding, Neda Jahanshad, Nenad Sestan, Zdenka Pausova, Sudha Seshadri, Tomas Paus

Date Published: 1st Jun 2020

Publication Type: Journal article

Genome-wide analysis of carotid plaque burden suggests a role of IL5 in men.
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Carotid artery plaque is an established marker of subclinical atherosclerosis with pronounced sex-dimorphism. Here, we aimed to identify genetic variants associated with carotid plaque … burden (CPB) and to examine potential sex-specific genetic effects on plaque sizes. METHODS AND RESULTS: We defined six operationalizations of CPB considering plaques in common carotid arteries, carotid bulb, and internal carotid arteries. We performed sex-specific genome-wide association analyses for all traits in the LIFE-Adult cohort (n = 727 men and n = 550 women) and tested significantly associated loci for sex-specific effects. In order to identify causal genes, we analyzed candidate gene expression data for correlation with CPB traits and corresponding sex-specific effects. Further, we tested if previously reported SNP associations with CAD and plaque prevalence are also associated with CBP. We found seven loci with suggestive significance for CPB (p<3.33x10-7), explaining together between 6 and 13% of the CPB variance. Sex-specific analysis showed a genome-wide significant hit for men at 5q31.1 (rs201629990, beta = -0.401, p = 5.22x10-9), which was not associated in women (beta = -0.127, p = 0.093) with a significant difference in effect size (p = 0.008). Analyses of gene expression data suggested IL5 as the most plausible candidate, as it reflected the same sex-specific association with CPBs (p = 0.037). Known plaque prevalence or CAD loci showed no enrichment in the association with CPB. CONCLUSIONS: We showed that CPB is a complementary trait in analyzing genetics of subclinical atherosclerosis. We detected a novel locus for plaque size in men only suggesting a role of IL5. Several estrogen response elements in this locus point towards a functional explanation of the observed sex-specific effect.

Authors: J. Pott, F. Beutner, K. Horn, H. Kirsten, K. Olischer, K. Wirkner, M. Loeffler, M. Scholz

Date Published: 30th May 2020

Publication Type: Journal article

Human Diseases: cardiovascular system disease, atherosclerosis

VISEP V-VERL-join
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP V-PAT-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: ODM Data

VISEP V-PAT-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP V-VERL-join-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP haemo_join-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP haemo_join-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: ODM Data

VISEP haemo_join
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP Endpoint-ODM
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: ODM Data

VISEP Endpoint
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

VISEP Endpoint-SPSS
SepNet - German Competence Network Sepsis
No description specified

Creator: Markus Löffler

Submitter: René Hänsel

Data file type: Clinical Data

2 hidden items
Bulletin COVID-19 Leipzig 2021-03-18
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Anne Dietrich, Dirk Hasenclever, Matthias Horn, Yuri Kheifetz, Tyll Krüger, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-10-16
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Löffler, Markus Scholz, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

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Bulletin COVID-19 Leipzig 2020-06-30
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Löffler, Markus Scholz, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-05-28
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-05-04
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-04-26
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-04-13
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-04-19
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-04-07
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Sibylle Schirm

Submitter: Christoph Beger

Download
Bulletin COVID-19 Leipzig 2020-11-15
Task Force COVID-19 Leipzig, Genetical Statistics and Systems Biology

Summary of the current COVID-19 pandemic development in Leipzig and Saxony. This work was done as part of the NFDI4Health Task Force COVID-19 (nfdi4health.de). We gratefully acknowledge the financial support of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – Project Number 451265285.

nfdi4health.de

Creators: Holger Kirsten, Markus Scholz, Markus Löffler, Peter Ahnert, Matthias Horn, Yuri Kheifetz, Kolja Nenoff, Sibylle Schirm

Submitter: Christoph Beger

Download
NFDI4Health

NFDI4Health - the National Research Data Infrastructure for Personal Health Data - deals with data generated in clinical trials, epidemiological and public health studies. The collection and analysis of these data on health and disease status and important factors influencing it are an essential component for the development of new therapies, comprehensive care approaches and preventive measures in a modern health care system. Although these data already meet high content quality standards, they ...

Projects: Task Force COVID-19 Leipzig

Web page: https://www.nfdi4health.de

MII - Medical Informatics Initiative

The medical informatics initiative was created to close the gap between research and healthcare. All of Germany’s university hospitals have joined forces with research institutions, businesses, health insurers, and patient advocacy groups to create a framework that harnesses research findings to the direct benefit of patients. The German Federal Ministry of Education and Research (BMBF) is investing around 160 million euros in the programme through 2021. The digitisation of medicine is creating ...

Projects: SMITH - Smart Medical Information Technology for Healthcare, POLAR - Polypharmacy, Drug Interactions, Risks

Web page: https://www.medizininformatik-initiative.de/en

Epidemiology
No description specified

Projects: LIFE Heart, LIFE - Leipzig Research Center for Civilization Diseases, SepNet - German Competence Network Sepsis, GC-HNPCC - German Consortium for Hereditary Non-Polyposis Colorectal Cancer, GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer, LIFE Adult

Web page: Not specified

NHL
No description specified

Projects: HaematoSys - Systems biology of haematopoiesis and haematopoietic neoplasia, GLA - German Lymphoma Alliance

Web page: Not specified

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The Health Atlas is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

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