rs11718455 (ABHD5): Coronary Artery Disease Locus
Key takeaways
- rs11718455 near ABHD5 is linked to coronary artery disease risk, reaching the standard genome-wide significance threshold.
- The association was discovered in over 34,500 cases and 261,000 controls and replicated in approximately 88,000 additional cases.
- This variant is one of 161 CAD risk loci cataloged in a large UK Biobank and CARDIoGRAMplusC4D meta-analysis.
- The ALT allele reduces expression of SNRK in esophageal tissue and multiple uncharacterized transcripts in cultured fibroblasts.
- The ALT allele increases POMGNT2 expression in cultured fibroblasts.
Key takeaways
- rs11718455, near the ABHD5 gene and the RNU6-367P pseudogene locus, is associated with coronary artery disease (CAD) risk in a large genome-wide study.
- The discovery phase used UK Biobank data (34,541 cases, 261,984 controls), replicated in approximately 88,000 additional cases and 162,000 controls from CARDIoGRAMplusC4D.
- This variant is one of 161 genome-wide significant CAD loci cataloged in a combined UK Biobank and CARDIoGRAMplusC4D meta-analysis.
- The ALT allele reduces expression of SNRK in esophageal mucosa and multiple uncharacterized transcripts in cultured fibroblasts.
- The ALT allele increases POMGNT2 expression in cultured fibroblasts.
What the research says
rs11718455, located near the ABHD5 gene (a locus also annotated with the RNU6-367P pseudogene), was identified as a genome-wide significant CAD susceptibility locus in a two-stage meta-analysis combining UK Biobank (34,541 cases, 261,984 controls) with CARDIoGRAMplusC4D (88,192 cases, 162,544 controls). This locus is one of 161 total CAD loci cataloged in the study, of which 64 were novel findings at the time of publication; fine mapping across all 161 loci was performed to generate credible sets of candidate causal variants for functional follow-up. The study also reported that CAD genetic risk variants across the full pool of loci were associated with atrial fibrillation (an irregular heart rhythm), heart failure, and mortality, but that is a general finding for the set of loci as a whole and is not a reported finding specific to this variant.
Reported associations
- Coronary artery disease (CAD): Reached genome-wide significance (p < 5x10-8) in a meta-analysis combining UK Biobank and CARDIoGRAMplusC4D, with a combined discovery and replication sample exceeding 122,000 cases and 424,000 controls; no per-variant effect size was provided in the available study text.
Evidence quality
The CAD association for this locus rests on a two-stage discovery-replication design: discovery in UK Biobank (34,541 cases, 261,984 controls) and replication in CARDIoGRAMplusC4D (88,192 cases, 162,544 controls), with genome-wide significance set at p < 5x10-8. No per-variant odds ratio or confidence interval was reported in the provided text, limiting quantitative interpretation. The study cataloged 161 CAD loci overall and noted that many candidate causal genes, especially among the 64 novel loci, had no obvious prior connection to CAD, underscoring that functional evidence for newer loci is still developing. Fine mapping was performed across all loci to produce credible variant sets, but independent external replication beyond the two cohorts described is not reported in the available text.
Tissue-specific expression effects
- POMGNT2: The ALT allele is associated with increased expression in cultured fibroblasts. GTEx Portal
- SNRK: The ALT allele is associated with reduced expression in esophageal mucosa (the inner lining of the esophagus). GTEx Portal
- Multiple uncharacterized transcripts (ENSG00000261786, ENSG00000280435, ENSG00000271192, ENSG00000272121, ENSG00000296421, ENSG00000297170): The ALT allele is associated with reduced expression of each of these transcripts in cultured fibroblasts. GTEx Portal
Lifestyle considerations
No lifestyle considerations on file for this variant.
Lifestyle context
Concrete actions anchored to the cited research. We do not prescribe, we describe.
Diet
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heart-healthy dietary pattern (Mediterranean-style) Moderate
Genetic CAD risk supports adoption of dietary patterns with evidence for cardiovascular protection
Emphasize vegetables, fruits, whole grains, legumes, fish; use olive oil; limit saturated fat and processed foods
Discuss with your doctor
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genetic contribution to coronary artery disease risk Moderate
T allele at rs11718455 (ABHD5) associated with increased CAD risk in large population cohort
Schedule discussion with primary care physician or cardiologist about genetic risk and personalized prevention plan
Exercise
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regular aerobic exercise for cardiovascular health Moderate
Increased genetic CAD risk supports evidence-based cardiovascular prevention through regular physical activity
Target 150 minutes per week moderate-intensity or 75 minutes vigorous-intensity aerobic activity
Screening
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coronary artery disease risk stratification and screening Moderate
Genetic risk variant warrants baseline CAD risk assessment and appropriate screening timeline based on total risk profile
Discuss timing and methods for CAD risk assessment with healthcare provider based on age and other risk factors
Frequently asked questions
What is rs11718455?
rs11718455 is a genetic variant near the ABHD5 gene and the RNU6-367P pseudogene that has been associated with coronary artery disease risk in a large genome-wide association study combining data from UK Biobank and CARDIoGRAMplusC4D.
Is rs11718455 linked to heart disease?
Yes. rs11718455 reached genome-wide significance for coronary artery disease in a meta-analysis that included over 120,000 cases and more than 420,000 controls across two large research cohorts.
What gene is near rs11718455?
rs11718455 is located near the ABHD5 gene and the RNU6-367P pseudogene. GTEx data shows the ALT allele alters expression of SNRK, POMGNT2, and several uncharacterized transcripts in fibroblasts and esophageal tissue.
How strong is the evidence for rs11718455 and coronary artery disease?
The association reached genome-wide significance (p < 5x10-8) in a two-stage discovery-replication design, but no per-variant effect size was reported in the available text. The study notes that functional evidence for many of its novel loci is still developing.
What does the rs11718455 ALT allele do to gene expression?
GTEx data shows the ALT allele increases POMGNT2 expression in cultured fibroblasts, reduces SNRK expression in esophageal mucosa, and reduces expression of six uncharacterized transcripts in fibroblasts.