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Article ; Online: KidneyGPS

Kira J. Stanzick / Klaus J. Stark / Mathias Gorski / Johannes Schödel / René Krüger / Florian Kronenberg / Richard Warth / Iris M. Heid / Thomas W. Winkler

BMC Bioinformatics, Vol 24, Iss 1, Pp 1-

a user-friendly web application to help prioritize kidney function genes and variants based on evidence from genome-wide association studies

2023 Volume 12

Abstract: Abstract Background Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent ... ...

Abstract	Abstract Background Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. Main Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects (“SNP-to-gene” mapping), (ii) genes with kidney phenotypes in mice or human (“gene-to-phenotype”), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function (“GPS tab”) to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data ( ...
Keywords	GWAS ; Kidney function ; Web application ; KidneyGPS ; Gene prioritization ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cardiovascular Risk Factor Control in 70- to 95-Year-Old Individuals

Ferdinand J. Donhauser / Martina E. Zimmermann / Anna B. Steinkirchner / Simon Wiegrebe / Alexander Dietl / Caroline Brandl / Ralph Burkhardt / André Gessner / Frank Schweda / Tobias Bergler / Elke Schäffner / Carsten A. Böger / Florian Kronenberg / Andreas Luchner / Klaus J. Stark / Iris M. Heid

Journal of Clinical Medicine, Vol 12, Iss 2102, p

Cross-Sectional Results from the Population-Based AugUR Study

2023 Volume 2102

Abstract: Cardiovascular risk factors such as high glucose, LDL-cholesterol, blood pressure, and impaired kidney function are particularly frequent in old-aged individuals. However, population-based data on the extent of cardiovascular risk factor control in the ... ...

Abstract	Cardiovascular risk factors such as high glucose, LDL-cholesterol, blood pressure, and impaired kidney function are particularly frequent in old-aged individuals. However, population-based data on the extent of cardiovascular risk factor control in the old-aged population is limited. AugUR is a cohort of the mobile “70+”-year-old population of/near Regensburg, recruited via population registries. We conducted cross-sectional analyses assessing the proportion of AugUR participants with LDL-cholesterol, HbA1c, or blood pressure beyond recommended levels and their association with impaired creatinine- and cystatin-based estimated glomerular filtration rate (eGFR, <60 mL/min/1.73 m 2 ) or urine albumin–creatinine ratio (UACR, ≥30 mg/g). Among 2215 AugUR participants, 74.7% were taking lipid-, glucose-, blood-pressure-lowering, or diuretic medication. High LDL-cholesterol at ≥116 mg/dL was observed for 76.1% (51.1% among those with prior cardiovascular events). We found HbA1c ≥ 7.0% for 6.3%, and high or low systolic blood pressure for 6.8% or 26.5%, respectively (≥160, <120 mmHg). Logistic regression revealed (i) high HbA1c levels associated with increased risk for impaired kidney function among those untreated, (ii) high blood pressure with increased UACR, and (iii) low blood pressure with impaired eGFR, which was confined to individuals taking diuretics. Our results provide important insights into cardiovascular risk factor control in individuals aged 70–95 years, which are understudied in most population-based studies.
Keywords	LDL-cholesterol ; HbA1c ; blood pressure ; estimated glomerular filtration rate ; urine albumin to creatinine ratio ; elderly population ; Medicine ; R
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Periodic breathing is associated with blood pressure above the recommended target in patients with type 2 diabetes

Andreas W. Schreib / Michael Arzt / Iris M. Heid / Bettina Jung / Carsten A. Böger / Stefan Stadler

Sleep Medicine: X, Vol 2, Iss , Pp 100013- (2020)

2020

Abstract: Background: Due to its prognostic importance for patients with type 2 diabetes (DM2), current guidelines recommend a systolic <130 mm Hg and diastolic <80 mm Hg blood pressure target. Periodic breathing, a form of sleep-disordered breathing, acutely ... ...

Abstract	Background: Due to its prognostic importance for patients with type 2 diabetes (DM2), current guidelines recommend a systolic <130 mm Hg and diastolic <80 mm Hg blood pressure target. Periodic breathing, a form of sleep-disordered breathing, acutely causes repetitive hypoxia, sympathetic nervous system activation as well as oscillations of heart rate and blood pressure. However, limited data on the association of periodic breathing and control of blood pressure (BP) in patients with DM2 are available. Thus, the aim of the present study was to assess whether there is an association between periodic breathing and increased BP above the recommended target in DM2. Methods: Cross-sectional data of 679 patients with DM2 from the DIACORE-SDB sub-study were analysed for association of periodic breathing with BP. Sleep-disordered breathing was assessed with a 2-channel ambulatory monitoring device including validated automatic pattern recognition for periodic breathing. BP values were determined in a standardized manner with three repeated measurements at rest. Results: Of the 679 analysed individuals (61% male, age 66 ± 9 years, Body Mass Index [BMI] 31.0 ± 5.4 kg/m2), 11% had periodic breathing. Patients with periodic breathing had significantly higher systolic BP values (144 ± 19 mm Hg vs. 137 ± 18 mm Hg, p = 0.003). Multivariable regression analysis revealed that periodic breathing was associated with higher systolic BP (B [95% confidence interval, CI] = 4.4 [0.1; 8.7], p = 0.043) and not meeting the recommended BP target for patients with diabetes (<130/80 mmHg) (odds ratio, OR [95%CI] = 2.1 [1.1; 4.0], p = 0.026) independent of sex, age, high density lipoproteins, renal function, coronary heart disease and antihypertensive treatment. Conclusion: Periodic breathing is associated with higher systolic BP in patients with DM2.
Keywords	Sleep-disordered breathing ; Periodic breathing ; Cheyne-stokes-respiration ; Systolic blood pressure ; Arterial hypertension ; Type 2 diabetes ; Specialties of internal medicine ; RC581-951
Subject code	515
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: IDGenerator

Matthias Olden / Rolf Holle / Iris M. Heid / Klaus Stark

BMC Medical Research Methodology, Vol 16, Iss 1, Pp 1-

unique identifier generator for epidemiologic or clinical studies

2016 Volume 10

Abstract: Abstract Background Creating study identifiers and assigning them to study participants is an important feature in epidemiologic studies, ensuring the consistency and privacy of the study data. The numbering system for identifiers needs to be random ... ...

Abstract	Abstract Background Creating study identifiers and assigning them to study participants is an important feature in epidemiologic studies, ensuring the consistency and privacy of the study data. The numbering system for identifiers needs to be random within certain number constraints, to carry extensions coding for organizational information, or to contain multiple layers of numbers per participant to diversify data access. Available software can generate globally-unique identifiers, but identifier-creating tools meeting the special needs of epidemiological studies are lacking. We have thus set out to develop a software program to generate IDs for epidemiological or clinical studies. Results Our software IDGenerator creates unique identifiers that not only carry a random identifier for a study participant, but also support the creation of structured IDs, where organizational information is coded into the ID directly. This may include study center (for multicenter-studies), study track (for studies with diversified study programs), or study visit (baseline, follow-up, regularly repeated visits). Our software can be used to add a check digit to the ID to minimize data entry errors. It facilitates the generation of IDs in batches and the creation of layered IDs (personal data ID, study data ID, temporary ID, external data ID) to ensure a high standard of data privacy. The software is supported by a user-friendly graphic interface that enables the generation of IDs in both standard text and barcode 128B format. Conclusion Our software IDGenerator can create identifiers meeting the specific needs for epidemiologic or clinical studies to facilitate study organization and data privacy. IDGenerator is freeware under the GNU General Public License version 3; a Windows port and the source code can be downloaded at the Open Science Framework website: https://osf.io/urs2g/ .
Keywords	Identifier ; ID ; ID generator ; ID creator ; Unique ; Barcode ; Medicine (General) ; R5-920
Subject code	005
Language	English
Publishing date	2016-09-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative Immunogenicity of COVID-19 Vaccines in a Population-Based Cohort Study with SARS-CoV-2-Infected and Uninfected Participants

David Peterhoff / Sebastian Einhauser / Stephanie Beileke / Hans-Helmut Niller / Felix Günther / Michael Schachtner / Benedikt Asbach / Philipp Steininger / Matthias Tenbusch / Antonia S. Peter / Andre Gessner / Ralph Burkhardt / Iris M. Heid / Ralf Wagner / Klaus Überla

Vaccines, Vol 10, Iss 324, p

2022 Volume 324

Abstract: To assess vaccine immunogenicity in non-infected and previously infected individuals in a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study ... ...

Abstract	To assess vaccine immunogenicity in non-infected and previously infected individuals in a real-world scenario, SARS-CoV-2 antibody responses were determined during follow-up 2 (April 2021) of the population-based Tirschenreuth COVID-19 cohort study comprising 3378 inhabitants of the Tirschenreuth county aged 14 years or older. Seronegative participants vaccinated once with Vaxzevria, Comirnaty, or Spikevax had median neutralizing antibody titers ranging from ID50 = 25 to 75. Individuals with two immunizations with Comirnaty or Spikevax had higher median ID50s (of 253 and 554, respectively). Regression analysis indicated that both increased age and increased time since vaccination independently decreased RBD binding and neutralizing antibody levels. Unvaccinated participants with detectable N-antibodies at baseline (June 2020) revealed a median ID50 of 72 at the April 2021 follow-up. Previously infected participants that received one dose of Vaxzevria or Comirnaty had median ID50 to 929 and 2502, respectively. Individuals with a second dose of Comirnaty given in a three-week interval after the first dose did not have higher median antibody levels than individuals with one dose. Prior infection also primed for high systemic IgA levels in response to one dose of Comirnaty that exceeded IgA levels observed after two doses of Comirnaty in previously uninfected participants. Neutralizing antibody levels targeting the spike protein of Beta and Delta variants were diminished compared to the wild type in vaccinated and infected participants.
Keywords	SARS-CoV-2 ; vaccination ; population-based cohort ; immunogenicity ; neutralizing antibodies ; Comirnaty ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions

Andreas Luchner / Ralph Burkhardt / Alexander Dietl / Martina E Zimmermann / Caroline Brandl / Stefan Wallner / Lars S Maier / Iris M Heid / Klaus J Stark

BMJ Open, Vol 11, Iss

cross-sectional results from the population-based AugUR study

2021 Volume 11

Keywords	Medicine ; R
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sleep apnoea and incident malignancy in type 2 diabetes

Sarah Driendl / Michael Arzt / Claudia S. Zimmermann / Bettina Jung / Tobias Pukrop / Carsten A. Böger / Sebastian Haferkamp / Florian Zeman / Iris M. Heid / Stefan Stadler

ERJ Open Research, Vol 7, Iss

2021 Volume 2

Abstract: Background Sleep apnoea and type 2 diabetes (T2D) have been linked to malignancy. The aim of the present study was to evaluate the association between sleep apnoea and incidence of malignancy in patients with T2D. Methods The DIACORE (DIAbetes COhoRtE) ... ...

Abstract	Background Sleep apnoea and type 2 diabetes (T2D) have been linked to malignancy. The aim of the present study was to evaluate the association between sleep apnoea and incidence of malignancy in patients with T2D. Methods The DIACORE (DIAbetes COhoRtE) study is a prospective, population-based cohort study in T2D patients. In the sleep disordered breathing substudy, the apnoea–hypopnoea index (AHI), oxygen desaturation index (ODI) and percentage of night-time spent with a peripheral oxygen saturation of <90% (tsat90%) were assessed using a two-channel ambulatory monitoring device. Malignancy diagnoses were gathered using self-reported medical history data validated by medical records. Hazard ratios (HRs) for incident malignancy were derived by Cox regression adjusting for sex, age, body mass index, smoking status, alcohol intake, socioeconomic status and HbA1c. Results Of 1239 patients with T2D (mean age 67 years, 41% female, mean body mass index 30.9 kg·m−2), 79 (6.4%) were first-time diagnosed with a malignancy within a median follow-up period of 2.7 years (interquartile range 2.2–4.5 years). AHI, ODI and tsat90% were not associated with incident malignancy. In subgroup analysis, females showed increased cancer risk per AHI unit (adjusted HR 1.03 per AHI unit, 95% CI 1.00–1.06; p=0.028) and severe sleep apnoea (defined as AHI ≥30 events·h−1; adjusted HR 4.19, 95% CI 1.39–12.77; p=0.012). This was not seen in males, and a significant interaction was observed (interaction terms p=0.048 and p=0.033, respectively). Conclusion Sleep apnoea was not associated with incident malignancy in T2D patients. However, stratified analysis revealed a significant association between sleep apnoea and incident malignancy in females, but not in males.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	European Respiratory Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spectrum Bias and Individual Strengths of SARS-CoV-2 Serological Tests—A Population-Based Evaluation

Sebastian Einhauser / David Peterhoff / Hans Helmut Niller / Stephanie Beileke / Felix Günther / Philipp Steininger / Ralph Burkhardt / Iris M. Heid / Annette B. Pfahlberg / Klaus Überla / Olaf Gefeller / Ralf Wagner

Diagnostics, Vol 11, Iss 1843, p

2021 Volume 1843

Abstract: Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 ... ...

Abstract	Antibody testing for determining the SARS-CoV-2 serostatus was rapidly introduced in early 2020 and since then has been gaining special emphasis regarding correlates of protection. With limited access to representative samples with known SARS-CoV-2 infection status during the initial period of test development and validation, spectrum bias has to be considered when moving from a “test establishment setting” to population-based settings, in which antibody testing is currently implemented. To provide insights into the presence and magnitude of spectrum bias and to estimate performance measures of antibody testing in a population-based environment, we compared SARS-CoV-2 neutralization to a battery of serological tests and latent class analyses (LCA) in a subgroup ( n = 856) of the larger population based TiKoCo-19 cohort ( n = 4185). Regarding spectrum bias, we could proof notable differences in test sensitivities and specificities when moving to a population-based setting, with larger effects visible in earlier registered tests. While in the population-based setting the two Roche ELECSYS anti-SARS-CoV-2 tests outperformed every other test and even LCA regarding sensitivity and specificity in dichotomous testing, they didn’t provide satisfying quantitative correlation with neutralization capacity. In contrast, our in-house anti SARS-CoV-2-Spike receptor binding domain (RBD) IgG-ELISA (enzyme-linked-immunosorbant assay) though inferior in dichotomous testing, provided satisfactory quantitative correlation and may thus represent a better correlate of protection. In summary, all tests, led by the two Roche tests, provided sufficient accuracy for dichotomous identification of neutralizing sera, with increasing spectrum bias visible in earlier registered tests, while the majority of tests, except the RBD-ELISA, didn’t provide satisfactory quantitative correlations.
Keywords	SARS-CoV-2 ; ELISA ; ECLIA ; neutralization ; spectrum bias ; serology ; Medicine (General) ; R5-920
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications

Thomas W Winkler / Felix Günther / Simon Höllerer / Martina Zimmermann / Ruth JF Loos / Zoltán Kutalik / Iris M Heid

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 13

Abstract: In GWAS, waist-to-hip ratio (WHR) is often adjusted for body mass index (BMI) to account for their correlation (WHRadjBMI). Here, Winkler et al. classify 159 genetic variants for BMI, WHR, or WHRadjBMI based on their effect directions for BMI and WHR to ... ...

Abstract	In GWAS, waist-to-hip ratio (WHR) is often adjusted for body mass index (BMI) to account for their correlation (WHRadjBMI). Here, Winkler et al. classify 159 genetic variants for BMI, WHR, or WHRadjBMI based on their effect directions for BMI and WHR to differentiate subtypes of adiposity genetics.
Keywords	Science ; Q
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Addendum

Thomas W Winkler / Felix Günther / Simon Höllerer / Martina Zimmermann / Ruth JF Loos / Zoltán Kutalik / Iris M Heid

Nature Communications, Vol 9, Iss 1, Pp 1-

A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications

2018 Volume 1

Keywords	Science ; Q
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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