From genotype to phenotype in human atherosclerosis - recent findings
Open accessAbstract
PURPOSE OF REVIEW: Since 2007, genome-wide association studies (GWAS) have led to the identification of numerous loci of atherosclerotic cardiovascular disease. The majority of these loci harbor genes previously not known to be involved in atherogenesis. In this review, we summarize the recent progress in understanding the pathophysiology of genetic variants in atherosclerosis. RECENT FINDINGS: Fifty-eight loci with P < 10⁻⁷ have been identified in GWAS for coronary heart disease and myocardial infarction. Of these, 23 loci (40%) overlap with GWAS loci of classical risk factors such as lipids, blood pressure, and diabetes mellitus, suggesting a potential causal relation. The vast majority of the remaining 35 loci (60%) are at genomic regions where the mechanism in atherogenesis is unclear. Loci most frequently found in independent GWAS were at Chr9p21.3 (ANRIL/CDKN2B-AS1), Chr6p24.1 (PHACTR1), and Chr1p13.3 (CELSR2, PSRC1, MYBPHL, SORT1). Recent work suggests that Chr9p21.3 exerts its effects through epigenetic regulation of target genes, whereas mechanisms at Chr6p24.1 remain obscure, and Chr1p13.3 affects plasma LDL cholesterol. SUMMARY: Novel GWAS loci indicate that our understanding of atherosclerosis is limited and implicate a role of hitherto unknown mechanisms, such as epigenetic gene regulation in atherogenesis.
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SNPs at the chromosome 9p21 locus are also associated with a number of other diseases, including coronary artery disease, in which ANRIL has previously been implicated.
“SNPs at the chromosome 9p21 locus are also associated with a number of other diseases, including coronary artery disease (CAD)—a disease in which ANRIL has previously been implicated55.”
From Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism (2017) · cites this paper as [55]
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Resequencing and Clinical Associations of the 9p21.3 Region
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Sapkota, Y., Steinthorsdottir, V., Morris, A. P., Fassbender, A., Rahmioglu, N., De Vivo, I., Buring, J. E., Zhang, F., Edwards, T. L., Jones, S., et al. (2017) · Nature Communications · doi:10.1038/ncomms15539 · Cited by 344 · see citing works
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- Authors
- Holdt, L. M., & Teupser, D.
- Affiliations
- Institut für Laboratoriumsmedizin (DE)
- LMU Klinikum (DE)
- Corresponding author
- Teupser, Daniel
- Venue
- Current Opinion in Lipidology
- Published
- 2013-10
- Volume
- 24
- Issue
- 5
- Pages
- 410-418
- ISSN
- 0957-9672 (ISSN-L)
- PMC
- PMC3814939
- OpenAlex
- W2065217448
- Cited by
- 62
- References
- 93
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 10 · 2017: 11 · 2016: 5 · 2015: 8 · 2014: 5 · 2013: 1
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-nd
- Locations
- Current Opinion in Lipidology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- atherosclerosis, atherosclerotic cardiovascular disease, coronary artery disease, myocardial infarction, genetic loci, genome-wide association study, PHACTR1, CELSR2, PSRC1, SORT1, epigenetic regulation, LDL cholesterol, genetic risk factors
- MeSH terms
- Chromosomes, Human, Genotype, Humans, Genome, Human, Epigenesis, Genetic, Atherosclerosis, Genome-Wide Association Study, Genetic Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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