IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29189-5.html
   My bibliography  Save this article

Genetic regulation of post-translational modification of two distinct proteins

Author

Listed:
  • Arianna Landini

    (University of Edinburgh)

  • Irena Trbojević-Akmačić

    (Genos Glycoscience Research Laboratory)

  • Pau Navarro

    (University of Edinburgh)

  • Yakov A. Tsepilov

    (Laboratory of Glycogenomics, Institute of Cytology and Genetics
    Novosibirsk State University)

  • Sodbo Z. Sharapov

    (Laboratory of Glycogenomics, Institute of Cytology and Genetics)

  • Frano Vučković

    (Genos Glycoscience Research Laboratory)

  • Ozren Polašek

    (School of Medicine, University of Split
    Algebra University College)

  • Caroline Hayward

    (University of Edinburgh)

  • Tea Petrović

    (Genos Glycoscience Research Laboratory)

  • Marija Vilaj

    (Genos Glycoscience Research Laboratory)

  • Yurii S. Aulchenko

    (Laboratory of Glycogenomics, Institute of Cytology and Genetics)

  • Gordan Lauc

    (Genos Glycoscience Research Laboratory
    University of Zagreb)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh)

  • Lucija Klarić

    (University of Edinburgh)

Abstract

Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins – glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.

Suggested Citation

  • Arianna Landini & Irena Trbojević-Akmačić & Pau Navarro & Yakov A. Tsepilov & Sodbo Z. Sharapov & Frano Vučković & Ozren Polašek & Caroline Hayward & Tea Petrović & Marija Vilaj & Yurii S. Aulchenko &, 2022. "Genetic regulation of post-translational modification of two distinct proteins," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29189-5
    DOI: 10.1038/s41467-022-29189-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29189-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29189-5?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. Alexander Lachmann & Denis Torre & Alexandra B. Keenan & Kathleen M. Jagodnik & Hoyjin J. Lee & Lily Wang & Moshe C. Silverstein & Avi Ma’ayan, 2018. "Massive mining of publicly available RNA-seq data from human and mouse," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    3. Yukihide Momozawa & Julia Dmitrieva & Emilie Théâtre & Valérie Deffontaine & Souad Rahmouni & Benoît Charloteaux & François Crins & Elisa Docampo & Mahmoud Elansary & Ann-Stephan Gori & Christelle Lec, 2018. "IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    4. B. Devlin & Kathryn Roeder, 1999. "Genomic Control for Association Studies," Biometrics, The International Biometric Society, vol. 55(4), pages 997-1004, December.
    5. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    6. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    7. Gordan Lauc & Jennifer E Huffman & Maja Pučić & Lina Zgaga & Barbara Adamczyk & Ana Mužinić & Mislav Novokmet & Ozren Polašek & Olga Gornik & Jasminka Krištić & Toma Keser & Veronique Vitart & Blanca , 2013. "Loci Associated with N-Glycosylation of Human Immunoglobulin G Show Pleiotropy with Autoimmune Diseases and Haematological Cancers," PLOS Genetics, Public Library of Science, vol. 9(1), pages 1-17, January.
    8. Beben Benyamin & Tonu Esko & Janina S. Ried & Aparna Radhakrishnan & Sita H. Vermeulen & Michela Traglia & Martin Gögele & Denise Anderson & Linda Broer & Clara Podmore & Jian’an Luan & Zoltan Kutalik, 2014. "Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    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. Seppe Goovaerts & Hanne Hoskens & Ryan J. Eller & Noah Herrick & Anthony M. Musolf & Cristina M. Justice & Meng Yuan & Sahin Naqvi & Myoung Keun Lee & Dirk Vandermeulen & Heather L. Szabo-Rogers & Pau, 2023. "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    5. Margaret Sunitha Selvaraj & Xihao Li & Zilin Li & Akhil Pampana & David Y. Zhang & Joseph Park & Stella Aslibekyan & Joshua C. Bis & Jennifer A. Brody & Brian E. Cade & Lee-Ming Chuang & Ren-Hua Chung, 2022. "Whole genome sequence analysis of blood lipid levels in >66,000 individuals," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Diptavo Dutta & Yuan He & Ashis Saha & Marios Arvanitis & Alexis Battle & Nilanjan Chatterjee, 2022. "Aggregative trans-eQTL analysis detects trait-specific target gene sets in whole blood," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. William R. Reay & Michael P. Geaghan & Murray J. Cairns, 2022. "The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. William J. Young & Najim Lahrouchi & Aaron Isaacs & ThuyVy Duong & Luisa Foco & Farah Ahmed & Jennifer A. Brody & Reem Salman & Raymond Noordam & Jan-Walter Benjamins & Jeffrey Haessler & Leo-Pekka Ly, 2022. "Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Ashley Budu-Aggrey & Anna Kilanowski & Maria K. Sobczyk & Suyash S. Shringarpure & Ruth Mitchell & Kadri Reis & Anu Reigo & Reedik Mägi & Mari Nelis & Nao Tanaka & Ben M. Brumpton & Laurent F. Thomas , 2023. "European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. 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.
    11. Eeva Sliz & Jaakko S. Tyrmi & Nilufer Rahmioglu & Krina T. Zondervan & Christian M. Becker & Outi Uimari & Johannes Kettunen, 2023. "Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    13. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    14. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    15. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    16. 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.
    17. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Magdalena Zimoń & Yunfeng Huang & Anthi Trasta & Aliaksandr Halavatyi & Jimmy Z. Liu & Chia-Yen Chen & Peter Blattmann & Bernd Klaus & Christopher D. Whelan & David Sexton & Sally John & Wolfgang Hube, 2021. "Pairwise effects between lipid GWAS genes modulate lipid plasma levels and cellular uptake," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    19. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    20. Keira J A Johnston & Joey Ward & Pradipta R Ray & Mark J Adams & Andrew M McIntosh & Blair H Smith & Rona J Strawbridge & Theodore J Price & Daniel J Smith & Barbara I Nicholl & Mark E S Bailey, 2021. "Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank," PLOS Genetics, Public Library of Science, vol. 17(4), pages 1-27, April.

    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:13:y:2022:i:1:d:10.1038_s41467-022-29189-5. 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: 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.