Identifying a Genetic Risk Factor for Sudden Cardiac Death
Author Information
Author(s): Arking Dan E., Junttila M. Juhani, Goyette Philippe, Huertas-Vazquez Adriana, Eijgelsheim Mark, Blom Marieke T., Newton-Cheh Christopher, Reinier Kyndaron, Teodorescu Carmen, Uy-Evanado Audrey, Carter-Monroe Naima, Kaikkonen Kari S., Kortelainen Marja-Leena, Boucher Gabrielle, Lagacé Caroline, Moes Anna, Zhao XiaoQing, Kolodgie Frank, Rivadeneira Fernando, Hofman Albert, Witteman Jacqueline C. M., Uitterlinden André G., Marsman Roos F., Pazoki Raha, Bardai Abdennasser, Koster Rudolph W., Dehghan Abbas, Hwang Shih-Jen, Bhatnagar Pallav, Post Wendy, Hilton Gina, Prineas Ronald J., Li Man, Köttgen Anna, Ehret Georg, Boerwinkle Eric, Coresh Josef, Kao W. H. Linda, Psaty Bruce M., Tomaselli Gordon F., Sotoodehnia Nona, Siscovick David S., Burke Greg L., Marbán Eduardo, Spooner Peter M., Cupples L. Adrienne, Jui Jonathan, Gunson Karen, Kesäniemi Y. Antero, Wilde Arthur A. M., Tardif Jean-Claude, O'Donnell Christopher J., Bezzina Connie R., Virmani Renu, Stricker Bruno H. C.
Primary Institution: Johns Hopkins University School of Medicine
Hypothesis
Can genetic variants modify susceptibility to sudden cardiac death (SCD) in individuals of European ancestry?
Conclusion
The study identified the BAZ2B locus as significantly associated with increased risk for sudden cardiac death.
Supporting Evidence
- The study involved a large sample size of over 30,000 individuals.
- Strong association was found with the BAZ2B locus, which was not previously implicated in SCD.
- The risk allele frequency was low, suggesting strong negative selection.
- QRS/QT interval-prolonging alleles were associated with increased risk for SCD.
- Findings highlight the genetic contribution to SCD susceptibility.
- Results were consistent across multiple independent studies.
- Identified loci may provide targets for future functional studies.
- Study design included both population-based and case-control studies.
Takeaway
Scientists found a gene that can make some people more likely to have sudden heart problems. This gene is rare but can double the risk of sudden cardiac death.
Methodology
The study performed a genome-wide association meta-analysis in 1,283 SCD cases and over 20,000 controls, followed by genotyping in additional samples.
Potential Biases
The inclusion of different control groups may introduce bias regarding the risk conferred by the BAZ2B locus.
Limitations
The study design may not identify the underlying functional variant at the loci, and the findings related to individual QRS/QT interval-prolonging alleles require further replication.
Participant Demographics
Participants were individuals of European ancestry.
Statistical Information
P-Value
1.8×10−10
Confidence Interval
95% CI 1.57–2.34
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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