Genetic associations with carotid intima-media thickness in the Chinese population and shared genetic architecture with cardiometabolic diseases and trait

Journal article

Background:
Carotid artery intima-media thickness (cIMT) is a highly heritable measure of subclinical atherosclerosis and a predictor of cardiovascular diseases. However, knowledge about their shared genetic basis remains limited. The majority of genome-wide association studies (GWASs) have been conducted in individuals of European ancestry, leaving the genetic determinants of cIMT in non-European ancestry populations largely understudied.
Methods:
A single-trait GWAS was performed in 22,370 participants from the China Kadoorie Biobank (CKB) to identify new genetic variants associated with cIMT. We then leveraged cIMT and cardiometabolic diseases and traits data from populations of European and East Asian ancestries, to conduct linkage disequilibrium score regression and genomewide cross-trait analysis, followed by gene-based analysis and Mendelian randomization (MR).
Results:
We identified 2 genome-wide significant loci for cIMT in the overall China Kadoorie Biobank analysis, including the known APOE locus and a novel locus at GGT5. In addition, a female-specific analysis identified a further novel locus at LINC02732. cIMT showed significant positive genetic correlations with coronary artery disease, type 2 diabetes, body mass index, and systolic blood pressure in both European and East Asian populations. Pleiotropic analysis found 110 and 699 significant pleiotropic variants in 4 trait pairs for East Asian and European populations, respectively, with 27 and 186 colocalized loci detected. Genebased analysis highlighted important biological pathways involving lipid metabolism and carbohydrate metabolism. Mendelian randomization estimates indicated that higher systolic blood pressure and body mass index, and coronary artery disease and type 2 diabetes, were causal for cIMT, and a reverse effect was observed between cIMT and systolic blood pressure.
Conclusion:
Our large-scale genome-wide association study of cIMT identified novel loci in Chinese population and shared genetic underpinnings and causal relationships with cardiometabolic diseases and traits. These findings potentially provide targets for intervention that may allow the development of new strategies targeting this aspect of atherosclerosis.

Authors: Wang, W; Huang, N; Yu, C; Sun, D; Pei, P

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Heart Association
• Journal: Circulation: Genomic and Precision Medicine
• Publication date: 2026-07-21
• Acceptance date: 2026-05-26
• DOI: 10.1161/CIRCGEN.125.005542
• EISSN: 2574-8300
• Language: English
• Keywords: blood pressure; carotid arteries; humans; lipid metabolism; Mendelian randomization analysis