ArticleCardiovascular research2022
Cis-epistasis at the LPA locus and risk of cardiovascular diseases.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Proteogenomics in human populations.Nature reviews. Genetics · 2026Review
- A practical guide to the management of dyslipidaemia.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Review
- Lipoprotein(a) and High-Risk Coronary Plaques: Mechanisms, Characteristics, and Emerging Therapeutic Strategies.Reviews in cardiovascular medicine · 2025Review
- Association of Lipoprotein A rs10455872 Polymorphism with Childhood Obesity and Obesity-Related Outcomes.Diagnostics (Basel, Switzerland) · 2025Article
- Epistasis regulates genetic control of cardiac hypertrophy.Nature cardiovascular research · 2025Article
- Epistasis in cardiac traits.Nature cardiovascular research · 2025Article
- Deciphering epistatic genetic regulation of cardiac hypertrophy.medRxiv : the preprint server for health sciences · 2025Article
- Lipoprotein(a) molar concentrations rather than genetic variants better predict coronary artery disease risk and severity in Han Chinese population.Lipids in health and disease · 2025Article
- FTO rs1121980 polymorphism contributes to coronary artery disease susceptibility in a Chinese Han population.Lipids in health and disease · 2025Article
- A scalable adaptive quadratic kernel method for interpretable epistasis analysis in complex traits.Genome research · 2024Article
- Epistasis regulates genetic control of cardiac hypertrophy.Research square · 2023Article
- Improving Genetic Association Studies with a Novel Methodology that Unveils the Hidden Complexity of All-Cause Heart Failure.medRxiv : the preprint server for health sciences · 2023Article
- Linking lifestyle factors to cardiovascular risk through metabolomics: Insights from a large population of diabetic patients followed-up for 11 years.Atherosclerosis · 2023Article
- Lipoprotein(a) beyond the kringle IV repeat polymorphism: The complexity of genetic variation in the LPA gene.Atherosclerosis · 2022Review
- The effect of LPA Thr3888Pro on lipoprotein(a) and coronary artery disease is modified by the LPA KIV-2 variant 4925G>A.Atherosclerosis · 2022Article
- Risk Prediction of Cardiovascular Events by Exploration of Molecular Data with Explainable Artificial Intelligence.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 17 institutions in 6 countries.
Funding
Abstract
aimsCoronary artery disease (CAD) has a strong genetic predisposition. However, despite substantial discoveries made by genome-wide association studies (GWAS), a large proportion of heritability awaits identification. Non-additive genetic effects might be responsible for part of the unaccounted genetic variance. Here, we attempted a proof-of-concept study to identify non-additive genetic effects, namely epistatic interactions, associated with CAD. METHODS AND
resultsWe tested for epistatic interactions in 10 CAD case-control studies and UK Biobank with focus on 8068 SNPs at 56 loci with known associations with CAD risk. We identified a SNP pair located in cis at the LPA locus, rs1800769 and rs9458001, to be jointly associated with risk for CAD [odds ratio (OR) = 1.37, P = 1.07 × 10-11], peripheral arterial disease (OR = 1.22, P = 2.32 × 10-4), aortic stenosis (OR = 1.47, P = 6.95 × 10-7), hepatic lipoprotein(a) (Lp(a)) transcript levels (beta = 0.39, P = 1.41 × 10-8), and Lp(a) serum levels (beta = 0.58, P = 8.7 × 10-32), while individual SNPs displayed no association. Further exploration of the LPA locus revealed a strong dependency of these associations on a rare variant, rs140570886, that was previously associated with Lp(a) levels. We confirmed increased CAD risk for heterozygous (relative OR = 1.46, P = 9.97 × 10-32) and individuals homozygous for the minor allele (relative OR = 1.77, P = 0.09) of rs140570886. Using forward model selection, we also show that epistatic interactions between rs140570886, rs9458001, and rs1800769 modulate the effects of the rs140570886 risk allele.
conclusionsThese results demonstrate the feasibility of a large-scale knowledge-based epistasis scan and provide rare evidence of an epistatic interaction in a complex human disease. We were directed to a variant (rs140570886) influencing risk through additive genetic as well as epistatic effects. In summary, this study provides deeper insights into the genetic architecture of a locus important for cardiovascular diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.