TY - GEN A1 - Monti, Remo A1 - Rautenstrauch, Pia A1 - Ghanbari, Mahsa A1 - Rani James, Alva A1 - Kirchler, Matthias A1 - Ohler, Uwe A1 - Konigorski, Stefan A1 - Lippert, Christoph T1 - Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät N2 - Here we present an exome-wide rare genetic variant association study for 30 blood biomarkers in 191,971 individuals in the UK Biobank. We compare gene- based association tests for separate functional variant categories to increase interpretability and identify 193 significant gene-biomarker associations. Genes associated with biomarkers were ~ 4.5-fold enriched for conferring Mendelian disorders. In addition to performing weighted gene-based variant collapsing tests, we design and apply variant-category-specific kernel-based tests that integrate quantitative functional variant effect predictions for mis- sense variants, splicing and the binding of RNA-binding proteins. For these tests, we present a computationally efficient combination of the likelihood- ratio and score tests that found 36% more associations than the score test alone while also controlling the type-1 error. Kernel-based tests identified 13% more associations than their gene-based collapsing counterparts and had advantages in the presence of gain of function missense variants. We introduce local collapsing by amino acid position for missense variants and use it to interpret associations and identify potential novel gain of function variants in PIEZO1. Our results show the benefits of investigating different functional mechanisms when performing rare-variant association tests, and demonstrate pervasive rare-variant contribution to biomarker variability. T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 16 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-586078 IS - 16 ER - TY - GEN A1 - Zenner, Alexander M. A1 - Böttinger, Erwin A1 - Konigorski, Stefan T1 - StudyMe BT - a new mobile app for user-centric N-of-1 trials T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät N2 - N-of-1 trials are multi-crossover self-experiments that allow individuals to systematically evaluate the effect of interventions on their personal health goals. Although several tools for N-of-1 trials exist, there is a gap in supporting non-experts in conducting their own user-centric trials. In this study, we present StudyMe, an open-source mobile application that is freely available from https://play.google.com/store/apps/details?id=health.studyu.me and offers users flexibility and guidance in configuring every component of their trials. We also present research that informed the development of StudyMe, focusing on trial creation. Through an initial survey with 272 participants, we learned that individuals are interested in a variety of personal health aspects and have unique ideas on how to improve them. In an iterative, user-centered development process with intermediate user tests, we developed StudyMe that features an educational part to communicate N-of-1 trial concepts. A final empirical evaluation of StudyMe showed that all participants were able to create their own trials successfully using StudyMe and the app achieved a very good usability rating. Our findings suggest that StudyMe provides a significant step towards enabling individuals to apply a systematic science-oriented approach to personalize health-related interventions and behavior modifications in their everyday lives. T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 18 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-589763 IS - 18 ER - TY - GEN A1 - Konigorski, Stefan A1 - Wernicke, Sarah A1 - Slosarek, Tamara A1 - Zenner, Alexander Maximilian A1 - Strelow, Nils A1 - Ruether, Darius Ferenc A1 - Henschel, Florian A1 - Manaswini, Manisha A1 - Pottbäcker, Fabian A1 - Edelman, Jonathan Antonio A1 - Owoyele, Babajide A1 - Danieletto, Matteo A1 - Golden, Eddye A1 - Zweig, Micol A1 - Nadkarni, Girish N. A1 - Bottinger, Erwin T1 - StudyU: A Platform for Designing and Conducting Innovative Digital N-of-1 Trials T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät N2 - N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available. Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app. With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice. T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 12 KW - digital interventions KW - N-of-1 trial KW - SCED KW - single-case experimental design KW - web application KW - mobile application KW - app KW - digital health Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-580370 IS - 12 ER -