articleNature CommunicationsJun 26, 2020GOLD OA

Genetic drug target validation using Mendelian randomisation

AFAmand F. SchmidtCFChris FinanMGMaría Gordillo‐MarañónFWFolkert W. AsselbergsDFDaniel F. Freitag

Heidelberg University · University Hospital Heidelberg · +8 more institutions

PubMed
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Abstract

Mendelian randomisation (MR) analysis is an important tool to elucidate the causal relevance of environmental and biological risk factors for disease. However, causal inference is undermined if genetic variants used to instrument a risk factor also influence alternative disease-pathways (horizontal pleiotropy). Here we report how the 'no horizontal pleiotropy assumption' is strengthened when proteins are the risk factors of interest. Proteins are typically the proximal effectors of biological processes encoded in the genome. Moreover, proteins are the targets of most medicines, so MR studies of drug targets are becoming a fundamental tool in drug development. To enable such studies, we introduce a mathematical…

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Topics & keywords

Topics
Keywords
  • Mendelian randomization
  • Pleiotropy
  • Computational biology
  • Inference
  • Robustness (evolution)
  • Mendelian inheritance
  • Disease
  • Computer science
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