IDEAS home Printed from https://ideas.repec.org/a/plo/pmed00/1003394.html
   My bibliography  Save this article

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author

Listed:
  • Ju-Sheng Zheng
  • Jian’an Luan
  • Eleni Sofianopoulou
  • Stephen J Sharp
  • Felix R Day
  • Fumiaki Imamura
  • Thomas E Gundersen
  • Luca A Lotta
  • Ivonne Sluijs
  • Isobel D Stewart
  • Rupal L Shah
  • Yvonne T van der Schouw
  • Eleanor Wheeler
  • Eva Ardanaz
  • Heiner Boeing
  • Miren Dorronsoro
  • Christina C Dahm
  • Niki Dimou
  • Douae El-Fatouhi
  • Paul W Franks
  • Guy Fagherazzi
  • Sara Grioni
  • José María Huerta
  • Alicia K Heath
  • Louise Hansen
  • Mazda Jenab
  • Paula Jakszyn
  • Rudolf Kaaks
  • Tilman Kühn
  • Kay-Tee Khaw
  • Nasser Laouali
  • Giovanna Masala
  • Peter M Nilsson
  • Kim Overvad
  • Anja Olsen
  • Salvatore Panico
  • J Ramón Quirós
  • Olov Rolandsson
  • Miguel Rodríguez-Barranco
  • Carlotta Sacerdote
  • Annemieke M W Spijkerman
  • Tammy Y N Tong
  • Rosario Tumino
  • Konstantinos K Tsilidis
  • John Danesh
  • Elio Riboli
  • Adam S Butterworth
  • Claudia Langenberg
  • Nita G Forouhi
  • Nicholas J Wareham

Abstract

Background: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p

Suggested Citation

  • Ju-Sheng Zheng & Jian’an Luan & Eleni Sofianopoulou & Stephen J Sharp & Felix R Day & Fumiaki Imamura & Thomas E Gundersen & Luca A Lotta & Ivonne Sluijs & Isobel D Stewart & Rupal L Shah & Yvonne T v, 2020. "The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis," PLOS Medicine, Public Library of Science, vol. 17(10), pages 1-21, October.
    • Handle: RePEc:plo:pmed00:1003394
    DOI: 10.1371/journal.pmed.1003394
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003394
    Download Restriction: no
    File URL: https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003394&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pmed.1003394?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. Guanghao Qi & Nilanjan Chatterjee, 2019. "Mendelian randomization analysis using mixture models for robust and efficient estimation of causal effects," Nature Communications, Nature, vol. 10(1), pages 1-10, 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. Yihe Yang & Noah Lorincz-Comi & Xiaofeng Zhu, 2023. "Unbiased estimation and asymptotically valid inference in multivariable Mendelian randomization with many weak instrumental variables," Papers 2301.05130, arXiv.org, revised Feb 2024.
    2. Ruoyu Wang & Qihua Wang & Wang Miao, 2023. "A robust fusion-extraction procedure with summary statistics in the presence of biased sources," Biometrika, Biometrika Trust, vol. 110(4), pages 1023-1040.
    3. Zhaotong Lin & Yangqing Deng & Wei Pan, 2021. "Combining the strengths of inverse-variance weighting and Egger regression in Mendelian randomization using a mixture of regressions model," PLOS Genetics, Public Library of Science, vol. 17(11), pages 1-25, November.
    4. Qing Cheng & Xiao Zhang & Lin S. Chen & Jin Liu, 2022. "Mendelian randomization accounting for complex correlated horizontal pleiotropy while elucidating shared genetic etiology," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Haoran Xue & Wei Pan, 2020. "Inferring causal direction between two traits in the presence of horizontal pleiotropy with GWAS summary data," PLOS Genetics, Public Library of Science, vol. 16(11), pages 1-30, November.
    6. 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.

    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:pmed00:1003394. 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: plosmedicine (email available below). General contact details of provider: https://journals.plos.org/plosmedicine/ .

    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.