Powerful and robust inference of complex phenotypes' causal genes with dependent expression quantitative loci by a median-based Mendelian randomization

Apr 23, 2022American journal of human genetics

Strong and reliable identification of genes causing complex traits using median-based Mendelian randomization with linked gene expression signals

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Abstract

The effective-median-based Mendelian randomization (EMIC) framework improves causal gene inference for complex phenotypes using GWAS summary statistics.

  • EMIC addresses high false-positive rates commonly seen in existing Mendelian randomization methods.
  • The method utilizes multiple cis-expression quantitative trait loci (eQTLs) to enhance causal gene inference accuracy.
  • In simulated datasets, EMIC demonstrated greater power for identifying causal genes compared to alternative approaches.
  • EMIC successfully rediscovered known causal genes associated with complex phenotypes like schizophrenia and bipolar disorder.
  • The framework also identified new candidate causal genes, expanding the understanding of genetic influences on complex traits.

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