Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke.

Autor: Zhang W; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Zhu J; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Wu X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Feng T; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Liao W; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Li X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Chen J; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Zhang L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Xiao C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China., Cui H; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Yang C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Yan P; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Wang Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Tang M; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Chen L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Liu Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Zou Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Wu X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Zhang L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.; Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, China., Yang C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Yao Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.; Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China., Li J; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China., Liu Z; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China., Jiang X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, West China- PUMC C. C. Chen Institute of Health, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China. xiajiang@scu.edu.cn.; Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. xiajiang@scu.edu.cn.; Department of Clinical Neuroscience, Karolinskaa Institutet, Stockholm, Sweden. xiajiang@scu.edu.cn., Zhang B; Hainan General Hospital and Hainan Affiliated Hospital, Hainan Medical University, Haikou, China; West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. wcsphwcfh@vip.163.com.
Jazyk: angličtina
Zdroj: Human genetics [Hum Genet] 2024 Oct; Vol. 143 (9-10), pp. 1131-1143. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1007/s00439-024-02666-1
Abstrakt: While carotid intima-media thickness (cIMT) as a noninvasive surrogate measure of atherosclerosis is widely considered a risk factor for stroke, the intrinsic link underlying cIMT and stroke has not been fully understood. We aimed to evaluate the clinical value of cIMT in stroke through the investigation of phenotypic and genetic relationships between cIMT and stroke. We evaluated phenotypic associations using observational data from UK Biobank (N = 21,526). We then investigated genetic relationships leveraging genomic data conducted in predominantly European ancestry for cIMT (N = 45,185) and any stroke (AS, N case /N control =40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMT max -AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMT mean -AS: HR = 1.39, 95%CI = 1.09-1.78; cIMT min -AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMT max -AS: [Formula: see text]=0.23, P=9.44 × 10 -5 ; cIMT mean -AS: [Formula: see text]=0.21, P=3.00 × 10 -4 ; cIMT min -AS: [Formula: see text]=0.16, P=6.30 × 10 -3 ). This was further substantiated by five shared independent loci and 15 shared expression-trait associations. Mendelian randomization analyses suggested no causal effect of cIMT on stroke (cIMT max -AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMT mean -AS: OR=1.09, 95%CI=0.93-1.26; cIMT min -AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMT max : beta=0.07, 95%CI = 0.01-0.13; AS-cIMT mean : beta=0.08, 95%CI = 0.01-0.15; AS-cIMT min : beta = 0.08, 95%CI = 0.01-0.16) in the reverse direction MR, which attenuated to non-significant in sensitivity analysis. Our work does not find evidence supporting causal associations between cIMT and stroke. The pronounced cIMT-stroke association is intrinsic, and mostly attributed to shared genetic components. The clinical value of cIMT as a surrogate marker for stroke risk in the general population is likely limited.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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