Sudden cardiac arrest (SCA) is a major public health concern, accounting for over 400,000 deaths in the US each year. While environmental factors clearly contribute to the determinants of SCA, familial aggregation studies and advances in the molecular genetics of inherited arrhythmias suggest that genetic factors confer susceptibility to SCA in the general population. Identifying these genetic factors will not only provide insight into the mechanisms of SCA, it will also have significant public health implications for risk stratification and prevention of SCA. We propose to systematically investigate the association of SCA and intermediate phenotypes with variations in biologically important molecular pathways involved in arrhythmogenesis using complete sequence information and haplotype analyses. Specifically, we will study the association of SCA risk with variation in candidate genes (Aim 1) that are proximal determinants of electrogenesis and propagation (e.g. cardiac ion channel genes and connexins) and genes in pathways that influence these proximal determinants (e.g. neurohumoral modulators). We will explore these associations in the context of the genetic and environmental milieu, investigating interactions with medications (Aim 2a), exercise (Aim 2b), and other genetic factors (Aim 2c). We will also examine main effects of genetic variation on intermediate quantitative phenotypes, such as ECG QT interval, heart rate, and heart rate variability (Aim 3). This application represents a multi-center collaborative effort to efficiently combine advances in genomics with material from four on-going studies that enable rigorous identification of the SCA phenotype or relevant intermediate phenotypes. Specifically, we will use material from a large population-based repository of SCA cases (Cardiac Arrest Blood Repository), two case-control studies (Cardiac Arrest Blood Study and Group Health Cooperative study), and a cohort study (Cardiovascular Health Study):

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-HOP-S (03))
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Wang, Lan-Hsiang
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University of Washington
Internal Medicine/Medicine
Schools of Medicine
United States
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Aliwarga, Theresa; Raccor, Brianne S; Lemaitre, Rozenn N et al. (2017) Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo. Free Radic Biol Med 112:131-140
Evans, Daniel S; Avery, Christy L; Nalls, Mike A et al. (2016) Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans. Hum Mol Genet 25:4350-4368
Mooney, Stephen J; Grady, Stephanie T; Sotoodehnia, Nona et al. (2016) In the Wrong Place with the Wrong SNP: The Association Between Stressful Neighborhoods and Cardiac Arrest Within Beta-2-adrenergic Receptor Variants. Epidemiology 27:656-62
Lemaitre, Rozenn N; Bartz, Traci M; King, Irena B et al. (2016) Circulating n-3 fatty acids and trans-fatty acids, PLA2G2A gene variation and sudden cardiac arrest. J Nutr Sci 5:e12
Wander, P L; Enquobahrie, D A; Pritchard, C C et al. (2016) Circulating microRNAs and sudden cardiac arrest outcomes. Resuscitation 106:96-101
Ghobrial, Joanna; Heckbert, Susan R; Bartz, Traci M et al. (2016) Ethnic differences in sudden cardiac arrest resuscitation. Heart 102:1363-70
Lemaitre, Rozenn N; Johnson, Catherine O; Hesselson, Stephanie et al. (2014) Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest. Heart Rhythm 11:471-7
Ilkhanoff, Leonard; Arking, Dan E; Lemaitre, Rozenn N et al. (2014) A common SCN5A variant is associated with PR interval and atrial fibrillation among African Americans. J Cardiovasc Electrophysiol 25:1150-7
Ritchie, Marylyn D; Denny, Joshua C; Zuvich, Rebecca L et al. (2013) Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk. Circulation 127:1377-85
Chen, Lin Y; Sotoodehnia, Nona; B?žková, Petra et al. (2013) Atrial fibrillation and the risk of sudden cardiac death: the atherosclerosis risk in communities study and cardiovascular health study. JAMA Intern Med 173:29-35

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