A Genome-First Study of Familial Hypercholesterolemia Comparing African and European Ancestry Individuals
Authors' conclusion
The prevalence of pathogenic variants did not significantly vary between African and European ancestry groups. VUSs were both more prevalent among individuals of African ancestry and associated with an increased risk of myocardial infarction equivalent to that of a pathogenic variant.
Study context
- Population
- Participants of All of Us, BioMe and MyCode (US cohorts); Familial hypercholesterolemia (FH) variants classified by ClinGen FH Variant Curation Expert Panel standards as pathogenic or VUS104,300 African ancestry
- Exposure
- African vs European ancestry
- Outcome
- Prevalence of FH pathogenic variant
Methodological detailsgenome-first, meta-analysis of 3 cohorts, multicentre, 3 US-based cohorts, adjusted for age and sex, meta-analysed across cohorts
- Genome-first, meta-analysis of 3 cohorts
- Multicentre
- 3 US-based cohorts
- Adjusted for age and sex
- Meta-analysed across cohorts
Main finding
As reported in the abstract
African ancestry
1 in 306
European ancestry
1 in 273
Observational data: associations, not effects.
Further findings
| Outcome | Difference (mg/dL) (95% CI) | |
|---|---|---|
| LDL-C elevation associated with pathogenic variantsGreater LDL-C elevation with pathogenic variant · adjusted for age and sex | 20.81 (16.17–25.45) | |
| LDL-C elevation associated with a VUSGreater LDL-C elevation with VUS | 10.01 (6.13–13.88) | |
| −2002040Difference, mg/dL (linear scale) |
| Outcome | OR (95% CI) | |
|---|---|---|
| MI risk with a VUS | 1.91 (1.18–3.10) | |
| 0.20.5125Odds ratio (log scale) |
| Outcome | Odds (95% CI) | P value |
|---|---|---|
| Having a VUSHigher odds of VUS | 1.61 (1.42–1.83) | P = 1.2×10-12 |
- MI risk with a VUS: VUS conferred increased MI risk only among African ancestry group
MI risk with a VUS
- Pathogenic variants in both ancestries conferred 2- to 3-fold increased MI risk
Original publication
A Genome-First Study of Familial Hypercholesterolemia Comparing African and European Ancestry Individuals. Circulation. Published 29 May 2026. doi:10.
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