Bidirectional Mendelian Randomisation Analysis Provides Evidence for the Causal Involvement of Dysregulation of CXCL9, CCL11 and CASP8 in the Pathogenesis of Ulcerative Colitis

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Bidirectional Mendelian Randomisation Analysis Provides Evidence for the Causal Involvement of Dysregulation of CXCL9, CCL11 and CASP8 in the Pathogenesis of Ulcerative Colitis

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.;Zhejiang Univ, Ctr Global Hlth, Sch Med, Hangzhou, Peoples R China.;Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, China; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China

Zhou, Yajing (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.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Sun, Yuhao (författare): Zhejiang Univ, Ctr Global Hlth, Sch Med, Hangzhou, Peoples R China.,Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, China

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Yuan, Shuai (författare): Karolinska Institutet

Kalla, Rahul (författare): Univ Edinburgh, Ctr Inflammat Res, Edinburgh IBD Sci Unit, Edinburgh, Scotland.,Edinburgh IBD Science Unit, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

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.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 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.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Wang, Lijuan (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.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Chen, Xuejie (författare): Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China.,Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China

Zhou, Xuan (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.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Dai, Siqi (författare): Zhejiang Univ, Affiliated Hosp 2, Key Lab Canc Prevent & Intervent, Colorectal Surg & Oncol,Sch Med,Minist Educ, Hangzhou, Zhejiang, Peoples R China.,Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China

Zhang, Yu (författare): Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gastroenterol, Coll Med, Hangzhou, Zhejiang, Peoples R China.,Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China

Ho, Gwo-tzer (författare): Edinburgh IBD Science Unit, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

Xia, Dajing (författare): Zhejiang Univ, Dept Toxicol, Sch Med, Sch Publ Hlth, Hangzhou, Zhejiang, Peoples R China.,Department of Toxicology of School of Public Health, & Center of Immunology & Infection, Zhejiang University School of Medicine, Hangzhou, China

Cao, Qian (författare): Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gastroenterol, Coll Med, Hangzhou, Zhejiang, Peoples R China.,Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, China

Liu, Zhanju (författare): Tongji Univ, Shanghai Peoples Hosp 10, Ctr IBD Res, Sch Med, Shanghai, Peoples R China.,Center for IBD Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China

Larsson, Susanna C. (författare): Karolinska Institutet,Uppsala universitet,Medicinsk epidemiologi,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden.,Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden

Wang, Xiaoyan (författare): Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China

Ding, Kefeng (författare): Zhejiang Univ, Affiliated Hosp 2, Sch Med, Hangzhou, Zhejiang, Peoples R China.,Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China

Halfvarson, Jonas, 1970- (författare): Örebro universitet,Institutionen för medicinska vetenskaper,Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden,Örebro Univ, Fac Med & Hlth, Dept Gastroenterol, Örebro, Sweden.

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.,Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Theodoratou, Evropi (författare): Univ Edinburgh, Usher Inst, Ctr Global Hlth, Edinburgh, Scotland.;Univ Edinburgh, Med Res Council Inst Genet & Canc, Canc Res UK Edinburgh Ctr, Edinburgh, Scotland.,Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK; Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK

Satsangi, Jack (författare): Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK

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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.;Zhejiang Univ, Ctr Global Hlth, Sch Med, Hangzhou, Peoples R China.;Cent South Univ, Xiangya Hosp 3, Dept Gastroenterol, Changsha, Peoples R China. Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, China; Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China (creator_code:org_t)

2022-12-28
2023
Engelska.
Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:5, s. 777-785

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...; https://urn.kb.se/re...; http://kipublication...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

Background and Aims Systemic inflammation is well recognised to be associated with ulcerative colitis [UC], but whether these effects are causal or consequential remains unclear. We aimed to define potential causal relationship of cytokine dysregulation with different tiers of evidence. Methods We first synthesised serum proteomic profiling data from two multicentred observational studies, in which a panel of systemic inflammatory proteins was analysed to examine their associations with UC risk. To further dissect observed associations, we then performed a bidirectional two-sample Mendelian randomisation [TSMR] analysis from both forward and reverse directions using five genome-wide association study [GWAS] summary level data for serum proteomic profiles and the largest GWAS of 28 738 European-ancestry individuals for UC risk. Results Pooled analysis of serum proteomic data identified 14 proteins to be associated with the risk of UC. Forward MR analysis using only cis-acting protein quantitative trait loci [cis-pQTLs] or trans-pQTLs further validated causal associations of two chemokines and the increased risk of UC: C-X-C motif chemokine ligand 9 [CXCL9] [OR 1.45, 95% CI 1.08, 1.95, p = 0.012] and C-C motif chemokine ligand 11 [CCL11] [OR 1.14, 95% CI 1.09, 1.18, p = 3.89 x 10(-10)]. Using both cis- and trans-acting pQTLs, an association of caspase-8 [CASP8] [OR 1.04, 95% CI 1.03, 1.05, p = 7.63 x 10(-19)] was additionally identified. Reverse MR did not find any influence of genetic predisposition to UC on any of these three inflammation proteins. Conclusion Pre-existing elevated levels of CXCL9, CCL11 and CASP8 may play a role in the pathogenesis of UC.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Systemic inflammatory proteins
ulcerative colitis
Mendelian randomisation

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