IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-022-35663-x.html
   My bibliography  Save this article

Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response

Author

Listed:
  • Koen F. Dekkers

    (Leiden University Medical Center)

  • Roderick C. Slieker

    (Leiden University Medical Center
    Amsterdam UMC, VUmc)

  • Andreea Ioan-Facsinay

    (Leiden University Medical Center)

  • Maarten Iterson

    (Leiden University Medical Center)

  • M. Arfan Ikram

    (Erasmus MC)

  • Marleen M. J. Greevenbroek

    (Maastricht University Medical Center)

  • Jan H. Veldink

    (Utrecht University)

  • Lude Franke

    (University Medical Center Groningen)

  • Dorret I. Boomsma

    (Vrije Universiteit Amsterdam)

  • P. Eline Slagboom

    (Leiden University Medical Center)

  • J. Wouter Jukema

    (Leiden University Medical Center
    Netherlands Heart Institute)

  • Bastiaan T. Heijmans

    (Leiden University Medical Center)

Abstract

Immune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain further insight in the molecular changes involved, we here perform a transcriptome-wide association analysis of blood triglycerides, HDL cholesterol, and LDL cholesterol in 3229 individuals, followed by a systematic bidirectional Mendelian randomization analysis to assess the direction of effects and control for pleiotropy. Triglycerides are found to induce transcriptional changes in 55 genes and HDL cholesterol in 5 genes. The function and cell-specific expression pattern of these genes implies that triglycerides downregulate both cellular lipid metabolism and, unexpectedly, allergic response. Indeed, a Mendelian randomization approach based on GWAS summary statistics indicates that several of these genes, including interleukin-4 (IL4) and IgE receptors (FCER1A, MS4A2), affect the incidence of allergic diseases. Our findings highlight the interplay between triglycerides and immune cells in allergic disease.

Suggested Citation

  • Koen F. Dekkers & Roderick C. Slieker & Andreea Ioan-Facsinay & Maarten Iterson & M. Arfan Ikram & Marleen M. J. Greevenbroek & Jan H. Veldink & Lude Franke & Dorret I. Boomsma & P. Eline Slagboom & J, 2023. "Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35663-x
    DOI: 10.1038/s41467-022-35663-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35663-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35663-x?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. Adam E. Locke & Bratati Kahali & Sonja I. Berndt & Anne E. Justice & Tune H. Pers & Felix R. Day & Corey Powell & Sailaja Vedantam & Martin L. Buchkovich & Jian Yang & Damien C. Croteau-Chonka & Tonu , 2015. "Genetic studies of body mass index yield new insights for obesity biology," Nature, Nature, vol. 518(7538), pages 197-206, February.
    2. Yukinori Okada & Di Wu & Gosia Trynka & Towfique Raj & Chikashi Terao & Katsunori Ikari & Yuta Kochi & Koichiro Ohmura & Akari Suzuki & Shinji Yoshida & Robert R. Graham & Arun Manoharan & Ward Ortman, 2014. "Genetics of rheumatoid arthritis contributes to biology and drug discovery," Nature, Nature, vol. 506(7488), pages 376-381, February.
    3. Eleonora Porcu & Marie C. Sadler & Kaido Lepik & Chiara Auwerx & Andrew R. Wood & Antoine Weihs & Maroun S. Bou Sleiman & Diogo M. Ribeiro & Stefania Bandinelli & Toshiko Tanaka & Matthias Nauck & Uwe, 2021. "Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome," Nature Communications, Nature, vol. 12(1), pages 1-9, 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. Pengfei Dong & Liting Song & Jaroslav Bendl & Ruth Misir & Zhiping Shao & Jonathan Edelstien & David A. Davis & Vahram Haroutunian & William K. Scott & Susanne Acker & Nathan Lawless & Gabriel E. Hoff, 2024. "A multi-regional human brain atlas of chromatin accessibility and gene expression facilitates promoter-isoform resolution genetic fine-mapping," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    4. Mary-Ellen Lynall & Blagoje Soskic & James Hayhurst & Jeremy Schwartzentruber & Daniel F. Levey & Gita A. Pathak & Renato Polimanti & Joel Gelernter & Murray B. Stein & Gosia Trynka & Menna R. Clatwor, 2022. "Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Yi Huang & Anyongqi Wang & Wenjiang Zhou & Baoguo Li & Linshan Zhang & Agata M. Rudolf & Zengguang Jin & Catherine Hambly & Guanlin Wang & John R. Speakman, 2024. "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Jie Huang & Jennifer E. Huffman & Yunfeng Huang & Ítalo Valle & Themistocles L. Assimes & Sridharan Raghavan & Benjamin F. Voight & Chang Liu & Albert-László Barabási & Rose D. L. Huang & Qin Hui & Xu, 2022. "Genomics and phenomics of body mass index reveals a complex disease network," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    7. Samuel Baker & Pietro Biroli & Hans van Kippersluis & Stephanie von Hinke, 2022. "Beyond Barker: Infant Mortality at Birth and Ischaemic Heart Disease in Older Age," Bristol Economics Discussion Papers 22/765, School of Economics, University of Bristol, UK.
    8. Parsa Akbari & Olukayode A. Sosina & Jonas Bovijn & Karl Landheer & Jonas B. Nielsen & Minhee Kim & Senem Aykul & Tanima De & Mary E. Haas & George Hindy & Nan Lin & Ian R. Dinsmore & Jonathan Z. Luo , 2022. "Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Viinikainen, Jutta & Bryson, Alex & Böckerman, Petri & Kari, Jaana T. & Lehtimäki, Terho & Raitakari, Olli & Viikari, Jorma & Pehkonen, Jaakko, 2022. "Does better education mitigate risky health behavior? A mendelian randomization study," Economics & Human Biology, Elsevier, vol. 46(C).
    10. Sarah Meulebrouck & Judith Merrheim & Gurvan Queniat & Cyril Bourouh & Mehdi Derhourhi & Mathilde Boissel & Xiaoyan Yi & Alaa Badreddine & Raphaël Boutry & Audrey Leloire & Bénédicte Toussaint & Souhi, 2024. "Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Duc-Hau Le, 2021. "A network-based method for predicting disease-associated enhancers," PLOS ONE, Public Library of Science, vol. 16(12), pages 1-20, December.
    12. Mateus H. Gouveia & Amy R. Bentley & Thiago P. Leal & Eduardo Tarazona-Santos & Carlos D. Bustamante & Adebowale A. Adeyemo & Charles N. Rotimi & Daniel Shriner, 2023. "Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    13. Sonali Pechlivanis & Susanne Moebus & Nils Lehmann & Raimund Erbel & Amir A Mahabadi & Per Hoffmann & Karl-Heinz Jöckel & Markus M Nöthen & Hagen S Bachmann & on behalf of the Heinz Nixdorf Recall Stu, 2020. "Genetic risk scores for coronary artery disease and its traditional risk factors: Their role in the progression of coronary artery calcification—Results of the Heinz Nixdorf Recall study," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-18, May.
    14. Emmanuel Cohen & Norbert Amougou & Amandine Ponty & Margaux Guerrien & Wakilongo Wakenge & Glory Chidumwa & Rihlat Said-Mohamed & Léopold K. Fezeu & Patrick Pasquet, 2022. "Direct and Indirect Determinants of Body Mass Index in Both Major Ethnic Groups Experiencing the Nutritional Transition in Cameroon," IJERPH, MDPI, vol. 19(10), pages 1-17, May.
    15. Vikesh Amin & Jere R. Behrman & Jason M. Fletcher & Carlos A. Flores & Alfonso Flores‐Lagunes & Hans‐Peter Kohler, 2021. "Genetic risks, adolescent health, and schooling attainment," Health Economics, John Wiley & Sons, Ltd., vol. 30(11), pages 2905-2920, November.
    16. Ada J. S. Chan & Worrawat Engchuan & Miriam S. Reuter & Zhuozhi Wang & Bhooma Thiruvahindrapuram & Brett Trost & Thomas Nalpathamkalam & Carol Negrijn & Sylvia Lamoureux & Giovanna Pellecchia & Rohan , 2022. "Genome-wide rare variant score associates with morphological subtypes of autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Marcin Kierczak & Nima Rafati & Julia Höglund & Hadrien Gourlé & Valeria Lo Faro & Daniel Schmitz & Weronica E. Ek & Ulf Gyllensten & Stefan Enroth & Diana Ekman & Björn Nystedt & Torgny Karlsson & Ås, 2022. "Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    18. Frank Windmeijer & Xiaoran Liang & Fernando P. Hartwig & Jack Bowden, 2021. "The confidence interval method for selecting valid instrumental variables," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 83(4), pages 752-776, September.
    19. Inga Petraviciene & Regina Grazuleviciene & Sandra Andrusaityte & Audrius Dedele & Mark J. Nieuwenhuijsen, 2018. "Impact of the Social and Natural Environment on Preschool-Age Children Weight," IJERPH, MDPI, vol. 15(3), pages 1-14, March.
    20. Kaitlyn A. Lagattuta & Hannah L. Park & Laurie Rumker & Kazuyoshi Ishigaki & Aparna Nathan & Soumya Raychaudhuri, 2024. "The genetic basis of autoimmunity seen through the lens of T cell functional traits," Nature Communications, Nature, vol. 15(1), pages 1-6, 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:14:y:2023:i:1:d:10.1038_s41467-022-35663-x. 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.