| Title: | Prevalence of FH-Causing Variants and Impact on LDL-C Concentration in European, South Asian, and African Ancestry Groups of the UK Biobank - Brief Report |
| Journal: | Arteriosclerosis Thrombosis and Vascular Biology |
| Published: | 6 Jul 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37409534/ |
| DOI: | https://doi.org/10.1161/atvbaha.123.319438 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.123.319438 |
Publication 11622
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Abstract
BACKGROUND: Familial hypercholesterolemia (FH) is a monogenic disease that causes high low-density lipoprotein cholesterol (LDL-C) and higher risk of premature coronary heart disease. The prevalence of FH-causing variants and their association with LDL-C in non-European populations remains largely unknown. Using DNA diagnosis in a population-based cohort, we aimed to estimate the prevalence of FH across 3 major ancestry groups in the United Kingdom.</p>
METHODS: Principal component analysis was used to distinguish genetic ancestry in UK Biobank participants. Whole exome sequencing data were analyzed to provide a genetic diagnosis of FH. LDL-C concentrations were adjusted for statin use.</p>
RESULTS: Principal component analysis distinguished 140 439 European, 4067 South Asian, and 3906 African participants with lipid and whole exome sequencing data. There were significant differences between the 3 groups, including total and LDL-C concentrations, and prevalence and incidence of coronary heart disease. We identified 488, 18, and 15 participants of European, South Asian, and African ancestry carrying a likely pathogenic or pathogenic FH-variant. No statistical difference in the prevalence of an FH-causing variant was observed: 1 out of 288 (95% CI, 1/316-1/264) in European, 1 out of 260 (95% CI, 1/526-1/173) in African, and 1 out of 226 (95% CI, 1/419-1/155) in South Asian. Carriers of an FH-causing variant had significantly higher LDL-C concentration than noncarriers in every ancestry group. There was no difference in median (statin-use adjusted) LDL-C concentration in FH-variant carriers depending on their ancestry background. Self-reported statin use was nonsignificantly highest in FH-variant carriers of South Asian ancestry (55.6%), followed by African (40.0%) and European (33.8%; P=0.15).</p>
CONCLUSIONS: The prevalence of FH-causing variants in the UK Biobank is similar across the ancestry groups analyzed. Despite overall differences in lipid concentrations, FH-variant carriers across the 3 ancestry groups had similar LDL-C levels. In all ancestry groups, the proportion of FH-variant carriers treated with lipid-lowering therapy should be improved to reduce future risk of premature coronary heart disease.</p>
3 Authors
- Jasmine Gratton
- Steve E. Humphries
- Marta Futema
1 Application
| Application ID | Title |
|---|---|
| 40721 | Low-density lipoprotein cholesterol (LDL-C) polygenic risk score and whole exome sequencing to diagnose individuals affected by familial hypercholesterolaemia |
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