Therapeutic targets for inflammatory bowel disease: proteome-wide Mendelian randomization and colocalization analyses

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Therapeutic targets for inflammatory bowel disease : proteome-wide Mendelian randomization and colocalization analyses

Chen, Jie (författare): Zhejiang Univ, Sch Publ Hlth, Sch Med, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.

Xu, Fengzhe (författare): Westlake Univ, Sch Life Sci, Key Lab Growth Regulat & Translat Res Zhejiang Pro, Hangzhou, Peoples R China.

Ruan, Xixian (författare): Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China.

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Sun, Jing (författare): Zhejiang Univ, Sch Publ Hlth, Sch Med, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.

Zhang, Yao (författare): Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gastroenterol, Sch Med, Shanghai, Peoples R China.

Zhang, Han (författare): Zhejiang Univ, Sch Publ Hlth, Sch Med, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.

Zhao, Jianhui (författare): Zhejiang Univ, Sch Publ Hlth, Sch Med, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.

Zheng, Jie (författare): Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Endocrine & Metab Dis, Dept Endocrine & Metab Dis,Sch Med, Shanghai, Peoples R China.

Larsson, Susanna C. (författare): Karolinska Institutet,Uppsala universitet,Medicinsk epidemiologi,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.

Wang, Xiaoyan (författare): Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China.

Li, Xue (författare): Zhejiang Univ, Sch Publ Hlth, Sch Med, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.

Yuan, Shuai (författare): Karolinska Institutet

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Zhejiang Univ, Sch Publ Hlth, Sch Med, Dept Big Data Hlth Sci, Hangzhou, Zhejiang, Peoples R China;Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China. Westlake Univ, Sch Life Sci, Key Lab Growth Regulat & Translat Res Zhejiang Pro, Hangzhou, Peoples R China. (creator_code:org_t)

Elsevier BV, 2023
2023
Engelska.
Ingår i: EBioMedicine. - : Elsevier BV. - 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...

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Background: Identifying new drug targets for inflammatory bowel disease (IBD) is urgently needed. The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) and colocalization analyses to identify possible targets for IBD.Methods: Summary-level data of 4907 circulating protein levels were extracted from a large-scale protein quantitative trait loci study including 35,559 individuals. Genetic associations with IBD and its subtypes were obtained from the Inflammatory Bowel Disease Genetics Consortium (25,024 cases and 34,915 controls), the FinnGen study (7206 cases and 253,199 controls), and the UK Biobank study (7045 cases and 449,282 controls). MR analysis was conducted to estimate the associations between protein and IBD risk. The colocalization analysis was used to examine whether the identified proteins and IBD shared casual variants.Findings: Genetically predicted levels of 3, and 5 circulating proteins were associated with IBD and ulcerative colitis (UC), respectively. With high supporting evidence of colocalization, genetically predicted MST1 (macrophage stim-ulating 1) and HGFAC (hepatocyte growth factor activator) levels were inversely associated with IBD risks. The as-sociations of STAT3 (signal transducer and activator of transcription 3), MST1, CXCL5 (C-X-C motif chemokine ligand 5), and ITPKA (inositol-trisphosphate 3-kinase A) with the risk of UC were supported by colocalization analysis.Interpretation: The proteome-wide MR investigation identified many proteins associated with the risk of IBD. MST1, HGFAC, STAT3, ITPKA, and CXCL5 deserve further investigation as potential therapeutic targets for IBD. 2023;89: Published https://doi.org/10. 1016/j.ebiom.2023. 104494

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Av författaren/redakt...: Chen, Jie; Xu, Fengzhe; Ruan, Xixian; Sun, Jing; Zhang, Yao; Zhang, Han; visa fler...; Zhao, Jianhui; Zheng, Jie; Larsson, Susanna ...; Wang, Xiaoyan; Li, Xue; Yuan, Shuai; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Gastroenterologi

Artiklar i publikationen: EBioMedicine

Av lärosätet: Uppsala universitet; Karolinska Institutet

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Therapeutic targets for inflammatory bowel disease : proteome-wide Mendelian randomization and colocalization analyses

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