Search: 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 (author)
- Karolinska Institutet
-
- Wang, Lijuan (author)
- 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 (author)
- Zhengzhou Univ, Coll Publ Hlth, Zhengzhou, Peoples R China.
-
show more...
-
- Xu, Fengzhe (author)
- Westlake Univ, Sch Life Sci, Key Lab Growth Regulat & Translat Res Zhejiang Pro, Hangzhou, Peoples R China.
-
- Zhou, Xuan (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
- Yu, Lili (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
- Sun, Jing (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
- Chen, Jie (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
- Ying, Haochao (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
- Xu, Xiaolin (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
- Yu, Yongfu (author)
- 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 (author)
- Univ Edinburgh, Usher Inst, Ctr Publ Hlth, Edinburgh, Scotland.
-
- Shen, Xia (author)
- 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 (author)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland.
-
- Gill, Dipender (author)
- 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 (author)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Scotland.
-
- Larsson, Susanna C. (author)
- Karolinska Institutet,Uppsala universitet,Medicinsk epidemiologi,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.
-
- Li, Xue (author)
- Zhejiang Univ, Sch Publ Hlth, Sch Med, Hangzhou, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China.
-
show less...
-
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
- English.
-
In: EBioMedicine. - : Elsevier. - 2352-3964. ; 89
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Autoimmune disease
- Mendelian randomization
- Colocalization
- Drug development
- TYK2
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Yuan, Shuai
-
Wang, Lijuan
-
Zhang, Han
-
Xu, Fengzhe
-
Zhou, Xuan
-
Yu, Lili
-
show more...
-
Sun, Jing
-
Chen, Jie
-
Ying, Haochao
-
Xu, Xiaolin
-
Yu, Yongfu
-
Spiliopoulou, At ...
-
Shen, Xia
-
Wilson, Jim
-
Gill, Dipender
-
Theodoratou, Evr ...
-
Larsson, Susanna ...
-
Li, Xue
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Basic Medicine
-
and Medical Genetics
- Articles in the publication
-
EBioMedicine
- By the university
-
Uppsala University
-
Karolinska Institutet