دورية أكاديمية
Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals
| العنوان: | Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals |
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| المؤلفون: | Dan E Arking, M Juhani Junttila, Philippe Goyette, Adriana Huertas-Vazquez, Mark Eijgelsheim, Marieke T Blom, Christopher Newton-Cheh, Kyndaron Reinier, Carmen Teodorescu, Audrey Uy-Evanado, Naima Carter-Monroe, Kari S Kaikkonen, Marja-Leena Kortelainen, Gabrielle Boucher, Caroline Lagacé, Anna Moes, XiaoQing Zhao, Frank Kolodgie, Fernando Rivadeneira, Albert Hofman, Jacqueline C M Witteman, André G Uitterlinden, Roos F Marsman, Raha Pazoki, Abdennasser Bardai, Rudolph W Koster, Abbas Dehghan, Shih-Jen Hwang, Pallav Bhatnagar, Wendy Post, Gina Hilton, Ronald J Prineas, Man Li, Anna Köttgen, Georg Ehret, Eric Boerwinkle, Josef Coresh, W H Linda Kao, Bruce M Psaty, Gordon F Tomaselli, Nona Sotoodehnia, David S Siscovick, Greg L Burke, Eduardo Marbán, Peter M Spooner, L Adrienne Cupples, Jonathan Jui, Karen Gunson, Y Antero Kesäniemi, Arthur A M Wilde, Jean-Claude Tardif, Christopher J O'Donnell, Connie R Bezzina, Renu Virmani, Bruno H C h Stricker, Hanno L Tan, Christine M Albert, Aravinda Chakravarti, John D Rioux, Heikki V Huikuri, Sumeet S Chugh |
| المجموعة: | RePEc (Research Papers in Economics) |
| الوصف: | Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). Author Summary: Family studies have clearly demonstrated a role for genes in modifying risk for sudden cardiac death (SCD), however genetic studies have been limited by available samples. Here we have assembled over 4,400 SCD cases with >30,000 controls, all of European ancestry, and utilize a two-stage study design. In the first stage, we conducted an unbiased genome-wide scan in 1,283 SCD cases and >20,000 controls, and then performed follow-up genotyping in the remainder of the samples. We demonstrate strong association to a region of the genome not previously implicated in SCD, the BAZ2B locus, which contains 3 genes not previously known to play a role in cardiac biology. In addition, we used the genome-wide scan data to test a focused hypothesis that genetic variants that modulate ECG traits associated with SCD (QT, QRS, and RR intervals) also modify risk for SCD, and we demonstrate that QT- and QRS-prolonging alleles are, as a group, associated with increased ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002158Test; https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002158&type=printableTest |
| DOI: | 10.1371/journal.pgen.1002158 |
| DOI: | 10.1371/journal.pgen.1002158&type=printable |
| الإتاحة: | https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002158Test https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002158&type=printableTest |
| رقم الانضمام: | edsbas.6F0CD5C1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pgen.1002158 |
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