| Title: | Phenotypic and genetic effect of carotid intima-media thickness on the risk of stroke |
| Journal: | Human Genetics |
| Published: | 5 Apr 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38578439/ |
| DOI: | https://doi.org/10.1007/s00439-024-02666-1 |
Publication 9956
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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, Ncase/Ncontrol=40,585/406,111). Observational analyses suggested an increased hazard of stroke per one standard deviation increase in cIMT (cIMTmax-AS: hazard ratio (HR) = 1.39, 95%CI = 1.09-1.79; cIMTmean-AS: HR = 1.39, 95%CI = 1.09-1.78; cIMTmin-AS: HR = 1.32, 95%CI = 1.04-1.68). A positive global genetic correlation was observed (cIMTmax-AS: $${r}_{g}$$=0.23, P=9.44 × 10−5; cIMTmean-AS: $${r}_{g}$$=0.21, P=3.00 × 10−4; cIMTmin-AS: $${r}_{g}$$=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 (cIMTmax-AS: odds ratio (OR)=1.12, 95%CI=0.97-1.28; cIMTmean-AS: OR=1.09, 95%CI=0.93-1.26; cIMTmin-AS: OR=1.03, 95%CI = 0.90-1.17). A putative association was observed for genetically predicted stroke on cIMT (AS-cIMTmax: beta=0.07, 95%CI = 0.01-0.13; AS-cIMTmean: beta=0.08, 95%CI = 0.01-0.15; AS-cIMTmin: 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.</p>
25 Authors
- Wenqiang Zhang
- Jingwei Zhu
- Xuan Wu
- Tianle Feng
- Wei Liao
- Xuan Li
- Jianci Chen
- Li Zhang
- Chenghan Xiao
- Huijie Cui
- Chao Yang
- Peijing Yan
- Yutong Wang
- Mingshuang Tang
- Lin Chen
- Yunjie Liu
- Yanqiu Zou
- Xueyao Wu
- Ling Zhang
- Chunxia Yang
- Yuqin Yao
- Jiayuan Li
- Zhenmi Liu
- Xia Jiang
- Ben Zhang
1 Application
| Application ID | Title |
|---|---|
| 50538 | Relationships between blood, urinary and other biomarkers and risk of human noncommunicable diseases, all-cause mortality, and cause-specific mortality |
Enabling scientific discoveries that improve human health