IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-020-20885-8.html
   My bibliography  Save this article

A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits

Author

Listed:
  • Christopher N. Foley

    (University of Cambridge
    University of Cambridge)

  • James R. Staley

    (University of Cambridge
    University of Bristol)

  • Philip G. Breen

    (University of Edinburgh, Kings Buildings)

  • Benjamin B. Sun

    (University of Cambridge)

  • Paul D. W. Kirk

    (University of Cambridge)

  • Stephen Burgess

    (University of Cambridge
    University of Cambridge)

  • Joanna M. M. Howson

    (University of Cambridge
    University of Cambridge and Cambridge University Hospitals
    Novo Nordisk Research Centre Oxford)

Abstract

Genome-wide association studies (GWAS) have identified thousands of genomic regions affecting complex diseases. The next challenge is to elucidate the causal genes and mechanisms involved. One approach is to use statistical colocalization to assess shared genetic aetiology across multiple related traits (e.g. molecular traits, metabolic pathways and complex diseases) to identify causal pathways, prioritize causal variants and evaluate pleiotropy. We propose HyPrColoc (Hypothesis Prioritisation for multi-trait Colocalization), an efficient deterministic Bayesian algorithm using GWAS summary statistics that can detect colocalization across vast numbers of traits simultaneously (e.g. 100 traits can be jointly analysed in around 1 s). We perform a genome-wide multi-trait colocalization analysis of coronary heart disease (CHD) and fourteen related traits, identifying 43 regions in which CHD colocalized with ≥1 trait, including 5 previously unknown CHD loci. Across the 43 loci, we further integrate gene and protein expression quantitative trait loci to identify candidate causal genes.

Suggested Citation

  • Christopher N. Foley & James R. Staley & Philip G. Breen & Benjamin B. Sun & Paul D. W. Kirk & Stephen Burgess & Joanna M. M. Howson, 2021. "A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20885-8
    DOI: 10.1038/s41467-020-20885-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-20885-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-20885-8?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
    ---><---

    Citations

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


    Cited by:

    1. David Stacey & Lingyan Chen & Paulina J. Stanczyk & Joanna M. M. Howson & Amy M. Mason & Stephen Burgess & Stephen MacDonald & Jonathan Langdown & Harriett McKinney & Kate Downes & Neda Farahi & James, 2022. "Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Karl Smith-Byrne & Åsa Hedman & Marios Dimitriou & Trishna Desai & Alexandr V. Sokolov & Helgi B. Schioth & Mine Koprulu & Maik Pietzner & Claudia Langenberg & Joshua Atkins & Ricardo Cortez Penha & J, 2024. "Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Fotios Koskeridis & Evangelos Evangelou & Saredo Said & Joseph J. Boyle & Paul Elliott & Abbas Dehghan & Ioanna Tzoulaki, 2022. "Pleiotropic genetic architecture and novel loci for C-reactive protein levels," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Xiaoguang Xu & Chachrit Khunsriraksakul & James M. Eales & Sebastien Rubin & David Scannali & Sushant Saluja & David Talavera & Havell Markus & Lida Wang & Maciej Drzal & Akhlaq Maan & Abigail C. Lay , 2024. "Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets," Nature Communications, Nature, vol. 15(1), pages 1-29, December.
    5. Maik Pietzner & Robert Lorenz Chua & Eleanor Wheeler & Katharina Jechow & Julian D. S. Willett & Helena Radbruch & Saskia Trump & Bettina Heidecker & Hugo Zeberg & Frank L. Heppner & Roland Eils & Mar, 2022. "ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Shufen Zheng & Philip S. Tsao & Cuiping Pan, 2024. "Abdominal aortic aneurysm and cardiometabolic traits share strong genetic susceptibility to lipid metabolism and inflammation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. N. Hernández & J. Soenksen & P. Newcombe & M. Sandhu & I. Barroso & C. Wallace & J. L. Asimit, 2021. "The flashfm approach for fine-mapping multiple quantitative traits," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    8. Benjamin B. Sun & Stephanie J. Loomis & Fabrizio Pizzagalli & Natalia Shatokhina & Jodie N. Painter & Christopher N. Foley & Megan E. Jensen & Donald G. McLaren & Sai Spandana Chintapalli & Alyssa H. , 2022. "Genetic map of regional sulcal morphology in the human brain from UK biobank data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    9. Michael G. Levin & Noah L. Tsao & Pankhuri Singhal & Chang Liu & Ha My T. Vy & Ishan Paranjpe & Joshua D. Backman & Tiffany R. Bellomo & William P. Bone & Kiran J. Biddinger & Qin Hui & Ozan Dikilitas, 2022. "Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Lingyan Chen & James E. Peters & Bram Prins & Elodie Persyn & Matthew Traylor & Praveen Surendran & Savita Karthikeyan & Ekaterina Yonova-Doing & Emanuele Angelantonio & David J. Roberts & Nicholas A., 2022. "Systematic Mendelian randomization using the human plasma proteome to discover potential therapeutic targets for stroke," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Derek W. Brown & Weiyin Zhou & Youjin Wang & Kristine Jones & Wen Luo & Casey Dagnall & Kedest Teshome & Alyssa Klein & Tongwu Zhang & Shu-Hong Lin & Olivia W. Lee & Sairah Khan & Jacqueline B. Vo & A, 2022. "Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    12. Jianxin Shi & Kouya Shiraishi & Jiyeon Choi & Keitaro Matsuo & Tzu-Yu Chen & Juncheng Dai & Rayjean J. Hung & Kexin Chen & Xiao-Ou Shu & Young Tae Kim & Maria Teresa Landi & Dongxin Lin & Wei Zheng & , 2023. "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20885-8. 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.

    We have no bibliographic references for this item. You can help adding them by using 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: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    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.