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Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome

Author

Listed:
  • Denis A Baird
  • Jimmy Z Liu
  • Jie Zheng
  • Solveig K Sieberts
  • Thanneer Perumal
  • Benjamin Elsworth
  • Tom G Richardson
  • Chia-Yen Chen
  • Minerva M Carrasquillo
  • Mariet Allen
  • Joseph S Reddy
  • Philip L De Jager
  • Nilufer Ertekin-Taner
  • Lara M Mangravite
  • Ben Logsdon
  • Karol Estrada
  • Philip C Haycock
  • Gibran Hemani
  • Heiko Runz
  • George Davey Smith
  • Tom R Gaunt
  • AMP-AD eQTL working group

Abstract

Discovering drugs that efficiently treat brain diseases has been challenging. Genetic variants that modulate the expression of potential drug targets can be utilized to assess the efficacy of therapeutic interventions. We therefore employed Mendelian Randomization (MR) on gene expression measured in brain tissue to identify drug targets involved in neurological and psychiatric diseases. We conducted a two-sample MR using cis-acting brain-derived expression quantitative trait loci (eQTLs) from the Accelerating Medicines Partnership for Alzheimer’s Disease consortium (AMP-AD) and the CommonMind Consortium (CMC) meta-analysis study (n = 1,286) as genetic instruments to predict the effects of 7,137 genes on 12 neurological and psychiatric disorders. We conducted Bayesian colocalization analysis on the top MR findings (using P

Suggested Citation

  • Denis A Baird & Jimmy Z Liu & Jie Zheng & Solveig K Sieberts & Thanneer Perumal & Benjamin Elsworth & Tom G Richardson & Chia-Yen Chen & Minerva M Carrasquillo & Mariet Allen & Joseph S Reddy & Philip, 2021. "Identifying drug targets for neurological and psychiatric disease via genetics and the brain transcriptome," PLOS Genetics, Public Library of Science, vol. 17(1), pages 1-26, January.
    • Handle: RePEc:plo:pgen00:1009224
    DOI: 10.1371/journal.pgen.1009224
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    1. Yang Wu & Jian Zeng & Futao Zhang & Zhihong Zhu & Ting Qi & Zhili Zheng & Luke R. Lloyd-Jones & Riccardo E. Marioni & Nicholas G. Martin & Grant W. Montgomery & Ian J. Deary & Naomi R. Wray & Peter M., 2018. "Integrative analysis of omics summary data reveals putative mechanisms underlying complex traits," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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