IDEAS home Printed from https://ideas.repec.org/a/plo/pgen00/1009224.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009224
    Download Restriction: no
    File URL: https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009224&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pgen.1009224?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Rodrigo R. R. Duarte & Oliver Pain & Matthew L. Bendall & Miguel Mulder Rougvie & Jez L. Marston & Sashika Selvackadunco & Claire Troakes & Szi Kay Leung & Rosemary A. Bamford & Jonathan Mill & Paul F, 2024. "Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhen Qiao & Julia Sidorenko & Joana A. Revez & Angli Xue & Xueling Lu & Katri Pärna & Harold Snieder & Peter M. Visscher & Naomi R. Wray & Loic Yengo, 2023. "Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Chris Wallace, 2021. "A more accurate method for colocalisation analysis allowing for multiple causal variants," PLOS Genetics, Public Library of Science, vol. 17(9), pages 1-11, September.
    3. Lei Li & Xuelian Ma & Ya Cui & Maxime Rotival & Wenyan Chen & Xudong Zou & Ruofan Ding & Yangmei Qin & Qixuan Wang & Lluis Quintana-Murci & Wei Li, 2023. "Immune-response 3′UTR alternative polyadenylation quantitative trait loci contribute to variation in human complex traits and diseases," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Alesha A. Hatton & Fei-Fei Cheng & Tian Lin & Ren-Juan Shen & Jie Chen & Zhili Zheng & Jia Qu & Fan Lyu & Sarah E. Harris & Simon R. Cox & Zi-Bing Jin & Nicholas G. Martin & Dongsheng Fan & Grant W. M, 2024. "Genetic control of DNA methylation is largely shared across European and East Asian populations," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Gianluca Ursini & Pasquale Di Carlo & Sreya Mukherjee & Qiang Chen & Shizhong Han & Jiyoung Kim & Maya Deyssenroth & Carmen J. Marsit & Jia Chen & Ke Hao & Giovanna Punzi & Daniel R. Weinberger, 2023. "Prioritization of potential causative genes for schizophrenia in placenta," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Yordi J. Vegte & Ruben N. Eppinga & M. Yldau Ende & Yanick P. Hagemeijer & Yuvaraj Mahendran & Elias Salfati & Albert V. Smith & Vanessa Y. Tan & Dan E. Arking & Ioanna Ntalla & Emil V. Appel & Claudi, 2023. "Genetic insights into resting heart rate and its role in cardiovascular disease," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    7. Jayshree Advani & Puja A. Mehta & Andrew R. Hamel & Sudeep Mehrotra & Christina Kiel & Tobias Strunz & Ximena Corso-Díaz & Madeline Kwicklis & Freekje Asten & Rinki Ratnapriya & Emily Y. Chew & Dena G, 2024. "QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    8. Marie C. Sadler & Chiara Auwerx & Kaido Lepik & Eleonora Porcu & Zoltán Kutalik, 2022. "Quantifying the role of transcript levels in mediating DNA methylation effects on complex traits and diseases," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Fengzhe Xu & Evan Yi-Wen Yu & Xue Cai & Liang Yue & Li-peng Jing & Xinxiu Liang & Yuanqing Fu & Zelei Miao & Min Yang & Menglei Shuai & Wanglong Gou & Congmei Xiao & Zhangzhi Xue & Yuting Xie & Sainan, 2023. "Genome-wide genotype-serum proteome mapping provides insights into the cross-ancestry differences in cardiometabolic disease susceptibility," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pgen00:1009224. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosgenetics (email available below). General contact details of provider: https://journals.plos.org/plosgenetics/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.