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  • Yu, LiliZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)

GDF-15 as a Therapeutic Target of Diabetic Complications Increases the Risk of Gallstone Disease : Mendelian Randomization and Polygenic Risk Score Analysis

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2022-06-13
  • Frontiers Media S.A.2022
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-481276
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-481276URI
  • https://doi.org/10.3389/fgene.2022.814457DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150075542URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Growth differentiation factor 15 (GDF-15) levels have been revealed as a robust biomarker for metformin use. We conducted Mendelian randomization (MR) analysis to explore the association between GDF-15 and gallstone disease to inform potential therapeutic effects targeting GDF-15. Four genetic variants associated with GDF-15 levels at p < 5 x 10(-8) were selected as instrumental variables from a genome-wide association meta-analysis including 21,758 individuals. Two-sample MR analysis was conducted using summary-level data from UK Biobank (10,520 gallstone cases and 350,674 controls) and FinnGen consortium (19,023 gallstone cases and 195,144 controls). Polygenic risk score analysis using individual-level data in UK biobank was performed to complement the MR findings by examining the non-linearity of the association. Diabetic complications were taken as positive controls to validate the therapeutic effect of targeting GDF-15. Linear and nonlinear associations between genetically predicted GDF-15 levels and gallstones were estimated with stratification by the diabetic status. In the two-sample MR analysis, the odds ratio (OR) of gallstones was 1.09 (95% confidence interval (CI), 1.03-1.15; p = 0.001) for one standard deviation increase in genetically predicted GDF-15 levels in the meta-analysis of two datasets. Polygenic risk score analysis found this association to be U-shaped (p = 0.037). The observed association was predominantly seen in nondiabetic population (OR = 1.11, 95% CI: 1.01-1.21; p = 0.003). An inverse association between genetically predicted GDF-15 levels and diabetic complications (OR = 0.77, 95% CI: 0.62-0.96; p = 0.023) was observed, validating the potential therapeutic effects of targeting GDF-15 levels. This MR study indicates that the increased risk of gallstone disease should be taken into account when considering GDF-15 as a therapeutic target for diabetic complications.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Zhou, YajingZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)
  • Wang, LijuanZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)
  • Zhou, XuanZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)
  • Sun, JingZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)
  • Xiao, JiaruiZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)
  • Xu, XiaolinZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China. (författare)
  • Larsson, Susanna C.Karolinska Institutet,Uppsala universitet,Medicinsk epidemiologi,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.(Swepub:uu)susla720 (författare)
  • Yuan, ShuaiKarolinska Institutet (författare)
  • Li, XueZhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China.;Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland. (författare)
  • Zhejiang Univ, Affiliated Hosp 2, Ctr Clin Big Data & Analyt, Dept Big Data Hlth Sci,Sch Publ Hlth,Sch Med, Hangzhou, Peoples R China.Medicinsk epidemiologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Frontiers in Genetics: Frontiers Media S.A.131664-8021

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