| Title: | Genetic susceptibility to infectious disease-associated adverse cardiac structure and function: a UK Biobank and ARIC imaging-genetics study |
| Journal: | BMJ Connections Clinical Genetics and Genomics |
| Published: | 26 Mar 2026 |
| DOI: | https://doi.org/10.1136/bmjccgg-2025-000027 |
| URL: | https://connectionscgg.bmj.com/content/3/1/e000027.full.pdf |
Publication 18192
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Abstract
Introduction Infections and cardiovascular disease (CVD) often co-occur; whether inherited liability to infection is associated with cardiac structure and function is unknown. Methods White adults without diagnosed infection from UK Biobank imaging (30 766) and Atherosclerosis Risk in Communities (ARIC) visit 5 (2546) were analysed. Genome-wide polygenic risk scores (PRSs) for infectious disease were related to cardiac MRI or echocardiography by principal component and Huber-robust regressions adjusted for age, sex and ancestry. Gene-set PRS (transforming growth factor-β (TGF-β), acute inflammation), cross-trait linkage-disequilibrium score (LDSC) regression and life-table modelling explored mechanisms, heritability and life-years lost. Results In UK Biobank, each SD increase in PRS reduced cardiac size (principal component (PC1) β=−0.06±0.01, p=7.7×10⁻⁸). Per-SD changes included right ventricular (RV) end-diastolic volume (RVEDV) index −0.27 (95% CI −0.34 to −0.19) and left ventricular (LV) stroke volume −0.14 (−0.23 to −0.06), both p<0.001. ARIC confirmed smaller LV end-diastolic volume (β=−0.45, p=0.039) and mass (β = −0.28, p=0.047). TGF-β and inflammation PRS each predicted adverse PC1 (β=−0.025, p<0.05). LDSC showed overlap between infection and RVEDV (r g =−0.06, p=0.002), LV stroke volume (r g =−0.07, p=0.021) and RV stroke volume (r g =−0.08, p=0.006). Highest versus lowest PRS tertile lost 7.9 life-years in men and 8.1 in women; CVD explained 5.3 and 5.5 years. Conclusions Genetic predisposition to infection is associated with smaller, stiffer hearts, with findings consistent with involvement of TGF-β and inflammatory pathways; it shares heritability with ventricular volumes and is associated with shorter life expectancy driven largely by cardiovascular deaths. Because the infectious-disease PRS was derived from genome-wide association study (GWAS) conducted predominantly in white populations, all PRS analyses were restricted to participants of white European ancestry in both UK Biobank and ARIC. </p>
9 Authors
- Jiazhen Zheng
- Haowen Chen
- Haisheng Wu
- Wenbo Huang
- Qiang Tu
- Junchun Shen
- Shuai Wang
- Shaojun Tang
- Gregory Y H Lip
1 Application
| Application ID | Title |
|---|---|
| 97089 | Associations of physical multimorbidity patterns and heart structure with cognition and neuroimaging outcomes |
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