ArticleHuman molecular genetics2015
Evidence for several independent genetic variants affecting lipoprotein (a) cholesterol levels.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 4 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 4 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Genome-Wide Association Study HighlightsArteriosclerosis, thrombosis, and vascular biology · 2021Pooled it
- LPA Variants Are Associated With Residual Cardiovascular Risk in Patients Receiving Statins.Circulation · 2018 · on this mapPooled it
- Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium.Human molecular genetics · 2017Pooled it
- A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms.Journal of lipid research · 2017Pooled it
- Lipoprotein(a)-cholesterol levels estimated by vertical auto profile correlate poorly with Lp(a) mass in hyperlipidemic subjects: Implications for clinical practice interpretation of Lp(a)-mediated risk.Journal of clinical lipidologyTrial
- Ancestral Variation in Lp(a): Epidemiology, Isoform Diversity, and Testing.Current atherosclerosis reports · 2025Review
- Lepodisiran: From genetic targeting to cardiovascular promise: A detailed narrative review of the literature.World journal of cardiology · 2025Review
- Predictive value of lipoprotein(a) for left atrial thrombus or spontaneous echo contrast in non-valvular atrial fibrillation patients with low CHALipids in health and disease · 2024Article
- Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Association of Genetic Polymorphisms with Abdominal Aortic Aneurysm in the Processes of Apoptosis, Inflammation, and Cholesterol Metabolism.Medicina (Kaunas, Lithuania) · 2023Article
- Assessment of Apolipoprotein(a) Isoform Size Using Phenotypic and Genotypic Methods.International journal of molecular sciences · 2023Review
- Lipoprotein(a) beyond the kringle IV repeat polymorphism: The complexity of genetic variation in the LPA gene.Atherosclerosis · 2022Review
- A novel deletion mutation in the LPA gene in a middle-aged woman with ischaemic stroke.BMC medical genomics · 2021Article
- Shared genetic etiology and causality between body fat percentage and cardiovascular diseases: a large-scale genome-wide cross-trait analysis.BMC medicine · 2021Article
- Lack of Association ofDisease markers · 2021Article
- Investigation of a nonsense mutation located in the complex KIV-2 copy number variation region of apolipoprotein(a) in 10,910 individuals.Genome medicine · 2020Article
- A comprehensive map of single-base polymorphisms in the hypervariableJournal of lipid research · 2019Article
- The Association of SNPs Located in the CDKN2B-AS1 and LPA Genes With Carotid Artery Stenosis and Atherogenic Stroke.Frontiers in neurology · 2019Article
- Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.Nature communications · 2018Article
- A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study.European journal of human genetics : EJHG · 2018Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability = 0.68-0.98). However, causal mutations and functional validation of biological pathways modulating Lp(a) metabolism are lacking. We performed a genome-wide association scan to identify genetic variants associated with Lp(a)-cholesterol levels in the Old Order Amish. We confirmed a previously known locus on chromosome 6q25-26 and found Lp(a) levels also to be significantly associated with a SNP near the APOA5-APOA4-APOC3-APOA1 gene cluster on chromosome 11q23 linked in the Amish to the APOC3 R19X null mutation. On 6q locus, we detected associations of Lp(a)-cholesterol with 118 common variants (P = 5 × 10(-8) to 3.91 × 10(-19)) spanning a ∼5.3 Mb region that included the LPA gene. To further elucidate variation within LPA, we sequenced LPA and identified two variants most strongly associated with Lp(a)-cholesterol, rs3798220 (P = 1.07 × 10(-14)) and rs10455872 (P = 1.85 × 10(-12)). We also measured copy numbers of kringle IV-2 (KIV-2) in LPA using qPCR. KIV-2 numbers were significantly associated with Lp(a)-cholesterol (P = 2.28 × 10(-9)). Conditional analyses revealed that rs3798220 and rs10455872 were associated with Lp(a)-cholesterol levels independent of each other and KIV-2 copy number. Furthermore, we determined for the first time that levels of LPA mRNA were higher in the carriers than non-carriers of rs10455872 (P = 0.0001) and were not different between carriers and non-carriers of rs3798220. Protein levels of apo(a) were higher in the carriers than non-carriers of both rs10455872 and rs3798220. In summary, we identified multiple independent genetic determinants for Lp(a)-cholesterol. These findings provide new insights into Lp(a) regulation.
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