| Title: | Mediation of Coronary Heart Disease Risk by Genetic, Socio-Environmental, and Lifestyle Factors Across Racial Groups |
| Journal: | American Journal of Preventive Cardiology |
| Published: | 1 Jan 2026 |
| DOI: | https://doi.org/10.1016/j.ajpc.2026.101409 |
Publication 16930
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Abstract
Background We investigated the extent to which differences in coronary heart disease (CHD) risk between self-identified race/ethnicity (SIRE) groups are mediated by genetic, socio-environmental, and lifestyle factors. Methods In UK Biobank, we estimated genetic susceptibility for CHD using a polygenic risk score (PRSCHD) based on 1.7 million single-nucleotide variants (PGS Catalog identification: PGS000018), and socio-environmental-lifestyle risk for CHD using a polysocial risk score (PSSCHD) based on 100 covariates. Using SIRE, participants were grouped as White or non-White (Asian/Asian British, Black/Black British, and Chinese). Incident CHD was defined as a composite of fatal and non-fatal myocardial infarction and coronary revascularization. Multivariable Cox regression and mediation analyses were performed. Results Of 382,475 participants (55.6±8.1 years, 57.5% female, 94.9% White, 1.7% Asian/Asian British, 1.6% Black/Black British, and 0.3% Chinese), 9,679 (2.5%) had an incident CHD event, during 10 years of follow-up. The adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for a 1 SD increase in PSSCHD, and PRSCHD for CHD risk were 1.32 (1.30 to 1.35, P<2×10−16), and 1.51 (1.48 to 1.55, P<2×10−16), respectively. Asian/Asian British participants had the highest cumulative incidence of CHD, followed by White, Black/Black British and Chinese participants. The adjusted HR for the risk of incident CHD in non-Whites was 1.33 (95% CIs: 1.20 to 1.48, P=1.0×10−7); 44% (95% CIs: 37 to 73%, P<2 ×10⁻¹⁶) of the association of non-White SIRE with incident CHD was mediated through PSSCHD whereas PRSCHD mediated 33% (95% CIs: 22 to 43%, P<2×10⁻¹⁶) of the association. In subgroup analyses, non-Whites had higher socio-environmental and lifestyle risk than Whites, while Asian/Asian British had the highest genetic susceptibility for CHD, followed by White, Black/Black British and Chinese individuals. Conclusions Socio-environmental and lifestyle factors had a stronger mediating effect than genetic factors on the association between SIRE and CHD in the UK Biobank. These findings advance our understanding of factors underlying differences in CHD risk across SIRE groups.</p>
5 Authors
- Mohammadreza Naderian
- Kristjan Norland
- Keyue Ding
- Ozan Dikilitas
- Iftikhar J. Kullo
1 Application
| Application ID | Title |
|---|---|
| 79990 | Development and validation of polygenic risk scores for coronary heart disease and related risk factors in diverse racial/ethnic groups |
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