A study of nearly 3,000 African American participants confirmed LPA as the central gene for Lp(a) levels — and explicitly warned that a much wider stretch of nearby genes looked significant only because of local genetic ancestry, not a real biological effect.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
Lipoprotein(a), abbreviated Lp(a), is a cholesterol-carrying particle in blood that is an independent risk factor for cardiovascular disease — its level is not reflected by a standard cholesterol panel, and it is determined overwhelmingly by genetics rather than diet or lifestyle. Lp(a) levels are, on average, substantially higher in African Americans than in European Americans, a population difference that turns out to matter directly for how this page's underlying study should be read.
Li et al. 2015 ran a genome- and exome-wide association study of Lp(a) in 2,895 African American participants in the Jackson Heart Study. The study found that local genetic ancestry at chromosome region 6q25.3 was itself an important risk factor for Lp(a) level. Before adjusting for that local ancestry, hundreds of SNPs spanning roughly 10 Mb around the well-established LPA gene reached statistical significance; after adjusting for local ancestry, the significant region narrowed sharply to under 1 Mb, centered squarely on LPA itself. A single coding variant in APOE was also significant, and a heavier burden of coding variants in both LPA and APOE was associated with higher Lp(a).
The paper's own conclusion is worth stating plainly, because it applies directly to this page: ancestry-specific causal variants sit in or near LPA, and most of the wider associations found before adjusting for ancestry are probably spurious — statistical artifacts of population structure rather than real biological effects. rs9355814, in LPA itself, is this page's direct match to the paper's central, non-spurious finding. Most of this page's other genes — ARID1B, RGS17, CNKSR3, SLC22A1, MAP3K4, and PARK2 — sit in that same broad chromosome 6q25-26 region the paper specifically flags as showing a wide, ancestry-confounded signal before adjustment. This page holds them because the GWAS Catalog record ties them to this study and trait, with the paper's own caveat about that region stated directly rather than left out.
One more study belongs here, not because a routine sweep found it, but because two of this site's own variants turned out to be its exact headline finding. Clarke et al. 2009, the PROCARDIS consortium, compared 3,145 coronary-disease cases against 3,352 controls, replicated in 4,846 more cases and 4,594 more controls. The study found two independent variants in LPA: rs10455872 (odds ratio 1.70 for coronary disease) and rs3798220 (odds ratio 1.92) — both already linked to higher Lp(a) level elsewhere on this site. People carrying both had an odds ratio of 2.57. The finding that matters most: once the analysis adjusted for Lp(a) level itself, the variants' association with coronary-disease risk disappeared — the textbook signature of a causal pathway running through the measured level, not a coincidence riding alongside it. This is genetic evidence, over a decade old, that lower Lp(a) should mean lower cardiovascular risk — which is exactly what made Novartis's pelacarsen trial newsworthy in 2026 when lowering Lp(a) pharmacologically did not lower cardiovascular events. The two findings are not in direct conflict — a drug and a population's inherited variation are different kinds of intervention — but the contrast is real and worth naming plainly rather than smoothing over.
2026-04-29 · Mass General Brigham Heart and Vascular Institute & Broad Institute of MIT and Harvard, published in JACC (245,394 All of Us participants; validated in a separate 53,306-person biobank cohort)
Researchers combined publicly available polygenic risk scores for 8 cardiovascular conditions (coronary artery disease, atrial fibrillation, type 2 diabetes, venous thromboembolism, thoracic aortic aneurysm, extreme hypertension, severe hypercholesterolemia, elevated Lp(a)) into one integrated report, trained on 245,394 All of Us participants and validated in a separate 53,306-person biobank. People in the top 10% of genetic risk were 3.7x more likely to develop coronary artery disease and 3.1x more likely to develop type 2 diabetes than those at average risk. The test is now clinically available through Mass General Brigham's Laboratory for Molecular Medicine and Broad Clinical Labs -- a risk score, not a diagnosis or treatment.
Lp(a) is measured directly with a blood test, not estimated from genotype, and no variant on this page is used clinically to diagnose elevated Lp(a) or guide treatment. High Lp(a) is an established, largely genetically determined cardiovascular risk factor that clinicians assess with a direct blood measurement — not with any of the variants on this page.
This page is unusual in explicitly naming a limitation in its own source study: several of the genes here sit in a region the paper itself describes as showing signals confounded by local genetic ancestry rather than confirmed biology. Readers should weigh LPA itself, the paper's central and adjustment-robust finding, more heavily than the other genes on this page.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Lipoprotein(a) Levels comes down to these specific, well-studied positions — not a diagnosis.
LPA · rs149302195
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 12 of 12 linked studies with a resolved discovery ancestry.
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Lipoprotein(a) Levels. MyGeneLog™. https://www.mygenelog.com/conditions/lipoprotein-a
Lipoprotein(a), or Lp(a), is a cholesterol-carrying particle in blood that is an independent cardiovascular disease risk factor, not reflected in a standard cholesterol panel, and determined largely by genetics.
In 2,895 African American participants, it confirmed LPA as the central gene for Lp(a) level after adjusting for local genetic ancestry — but before that adjustment, a much wider stretch of chromosome 6 appeared significant, which the paper itself calls likely spurious.
Because being direct about it matters: several of this page's genes sit in the wide chromosome region the paper specifically warns is confounded by ancestry rather than reflecting real biology. LPA itself is the paper's robust, adjustment-surviving finding.
No. Lp(a) is measured directly with a blood test. This page describes population-level genetic associations from one research study, not a predictive test.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.