SwePub
Sök i LIBRIS databas

  Utökad sökning

onr:"swepub:oai:DiVA.org:uu-500137"
 

Sökning: onr:"swepub:oai:DiVA.org:uu-500137" > Mendelian randomiza...

Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases

Yuan, Shuai (författare)
Karolinska Institutet
Wang, Lijuan (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.;Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland.
Zhang, Han (författare)
Zhengzhou Univ, Coll Publ Hlth, Zhengzhou, Peoples R China.
visa fler...
Xu, Fengzhe (författare)
Westlake Univ, Sch Life Sci, Key Lab Growth Regulat & Translat Res Zhejiang Pro, Hangzhou, Peoples R China.
Zhou, Xuan (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
Yu, Lili (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
Sun, Jing (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
Chen, Jie (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
Ying, Haochao (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
Xu, Xiaolin (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
Yu, Yongfu (författare)
Fudan Univ, Sch Publ Hlth, Dept Biostat, Shanghai, Peoples R China.;Fudan Univ, Key Lab Publ Hlth Safety, Minist Educ, Shanghai, Peoples R China.
Spiliopoulou, Athina (författare)
Univ Edinburgh, Usher Inst, Ctr Publ Hlth, Edinburgh, Scotland.
Shen, Xia (författare)
Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland.;Fudan Univ, Greater Bay Area Inst Precis Med Guangzhou, Ctr Intelligent Med Res, Guangzhou, Peoples R China.;Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China.
Wilson, Jim (författare)
Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland.
Gill, Dipender (författare)
Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. Cambridge Inst Publ Hlth, Med Res Council, Biostat Unit, Cambridge, England. Univ Edinburgh, Med Res Council, Canc Res UK Edinburgh Ctr, Inst Genet & Canc, Edinburgh, Scotland. Uppsala Univ, Dept Surg Sci, Unit Med Epidemiol, Uppsala, Sweden.
Theodoratou, Evropi (författare)
Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland.
Larsson, Susanna C. (författare)
Karolinska Institutet,Uppsala universitet,Medicinsk epidemiologi,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
Li, Xue (författare)
Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
visa färre...
Karolinska Institutet Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.;Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland. (creator_code:org_t)
Elsevier, 2023
2023
Engelska.
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 89
Relaterad länk:
https://doi.org/10.1...
visa fler...
https://uu.diva-port... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
http://kipublication...
visa färre...
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Background: To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing opportunities, adverse effects, and biomarkers of efficacy.Methods: The loss-of-function missense variant rs34536443 in TYK2 gene was used as a genetic instrument to proxy the effect of TYK2 inhibition. A phenome-wide Mendelian randomization (MR) study was conducted to explore the associations of genetically-proxied TYK2 inhibition with 1473 disease outcomes in UK Biobank (N = 339,197). Identified associations were examined for replication in FinnGen (N = 260,405). We further performed tissue -specific gene expression MR, colocalization analyses, and MR with 247 blood biomarkers. A systematic review of randomized controlled trials (RCTs) on TYK2 inhibitor was performed to complement the genetic evidence.Findings: PheWAS-MR found that genetically-proxied TYK2 inhibition was associated with lower risk of a wide range of autoimmune diseases. The associations with hypothyroidism and psoriasis were confirmed in MR analysis of tissue-specific TYK2 gene expression and the associations with systemic lupus erythematosus, psoriasis, and rheumatoid arthritis were observed in colocalization analysis. There were nominal associations of genetically-proxied TYK2 inhibition with increased risk of prostate and breast cancer but not in tissue-specific expression MR or colocalization analyses. Thirty-seven blood biomarkers were associated with the TYK2 loss-of-function mutation. Evidence from RCTs confirmed the effectiveness of TYK2 inhibitors on plaque psoriasis and reported several adverse effects.Interpretation: This study supports TYK2 inhibitor as a potential treatment for psoriasis and several other autoim-mune diseases. Increased pharmacovigilance is warranted in relation to the potential adverse effects.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Autoimmune disease
Mendelian randomization
Colocalization
Drug development
TYK2

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy