@misc{MontiRautenstrauchGhanbarietal.2022,
  author    = {Monti, Remo and Rautenstrauch, Pia and Ghanbari, Mahsa and Rani James, Alva and Kirchler, Matthias and Ohler, Uwe and Konigorski, Stefan and Lippert, Christoph},
  title     = {Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Reihe der Digital Engineering Fakult{\"a}t},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Reihe der Digital Engineering Fakult{\"a}t},
  number    = {16},
  doi       = {10.25932/publishup-58607},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-586078},
  pages     = {16},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@misc{KonigorskiWernickeSlosareketal.2021,
  author    = {Konigorski, Stefan and Wernicke, Sarah and Slosarek, Tamara and Zenner, Alexander Maximilian and Strelow, Nils and Ruether, Darius Ferenc and Henschel, Florian and Manaswini, Manisha and Pottb{\"a}cker, Fabian and Edelman, Jonathan Antonio and Owoyele, Babajide and Danieletto, Matteo and Golden, Eddye and Zweig, Micol and Nadkarni, Girish N. and Bottinger, Erwin},
  title     = {StudyU: A Platform for Designing and Conducting Innovative Digital N-of-1 Trials},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Reihe der Digital Engineering Fakult{\"a}t},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Reihe der Digital Engineering Fakult{\"a}t},
  number    = {12},
  doi       = {10.25932/publishup-58037},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-580370},
  pages     = {12},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}