| Title: | Ascertainment Bias in the Association Between Elevated Lipoprotein(a) and Familial Hypercholesterolemia |
| Journal: | Journal of the American College of Cardiology |
| Published: | 1 Jun 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32466883/ |
| DOI: | https://doi.org/10.1016/j.jacc.2020.03.065 |
Publication 3249
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Abstract
BACKGROUND: Lipoprotein(a) is an atherogenic low-density lipoprotein-like particle and circulating levels are largely determined by genetics. Patients with familial hypercholesterolemia (FH) have elevated lipoprotein(a); however, it remains unclear why.</p>
OBJECTIVES: This study compared the levels of lipoprotein(a) and associated genetic factors between individuals that were ascertained for FH clinically versus genetically.</p>
METHODS: We investigated causes of elevated lipoprotein(a) in individuals with clinically diagnosed FH (FH cohort, n = 391) and in individuals with genetically diagnosed FH from the general population (UK Biobank; n = 37,486).</p>
RESULTS: Patients in the FH cohort had significantly greater lipoprotein(a) levels than either the general population or non-FH dyslipidemic patients. This was accounted for by increased frequency of the rs10455872-G LPA risk allele (15.1% vs. 8.8%; p < 0.05). However, within the FH cohort, lipoprotein(a) levels did not differ based on the presence or absence of an FH-causing variant (means = 1.43 log mg/dl vs. 1.42 log mg/dl; p = 0.97). Lipoprotein(a) levels were also not statistically different between individuals with and without an FH-causing variant in the UK Biobank cohort, which represents a population sample not biased to cardiovascular ascertainment (n = 221 vs. 37,486). We performed a phenome-wide association study between LPA genotypes and 19,202 phenotypes to demonstrate that elevated lipoprotein(a) is associated with increased low-density lipoprotein cholesterol, a family history of cardiovascular disease, premature coronary artery disease, and a diagnosis of FH.</p>
CONCLUSIONS: These results suggest that FH does not cause elevated lipoprotein(a), but that elevated lipoprotein(a) increases the likelihood that an individual with genetic FH will be clinically recognized.</p>
11 Keywords
- Adult
- Aged
- Alleles
- Cohort Studies
- Female
- Humans
- Hyperlipoproteinemia Type II
- Lipoprotein(a)
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
9 Authors
- Mark Trinder
- Maria L. DeCastro
- Hawmid Azizi
- Luba Cermakova
- Linda M. Jackson
- Jiri Frohlich
- G.B. John Mancini
- Gordon A. Francis
- Liam R. Brunham
1 Application
| Application ID | Title |
|---|---|
| 42857 | Influence of plasma lipoprotein genetics on infectious disease outcomes |
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