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Genome-wide association studies of the PR interval in African Americans
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نویسنده
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smith j.g. ,magnani j.w. ,palmer c. ,meng y.a. ,soliman e.z. ,musani s.k. ,kerr k.f. ,schnabel r.b. ,lubitz s.a. ,sotoodehnia n. ,redline s. ,pfeufer a. ,müller m. ,evans d.s. ,nalls m.a. ,liu y. ,newman a.b. ,zonderman a.b. ,evans m.k. ,deo r. ,ellinor p.t. ,paltoo d.n. ,newton-cheh c. ,benjamin e.j. ,mehra r. ,alonso a. ,heckbert s.r. ,fox e.r.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 2
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چکیده
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The pr interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. the pr interval is heritable,provides important information about arrhythmia risk,and has been suggested to differ among human races. genome-wide association (gwa) studies have identified common genetic determinants of the pr interval in individuals of european and asian ancestry,but there is a general paucity of gwa studies in individuals of african ancestry. we performed gwa studies in african american individuals from four cohorts (n = 6,247) to identify genetic variants associated with pr interval duration. genotyping was performed using the affymetrix 6.0 microarray. imputation was performed for 2.8 million single nucleotide polymorphisms (snps) using combined yri and ceu hapmap phase ii panels. we observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (scn5a) with genome-wide significant association (p<2.5×10-8) in two of the four cohorts and in the meta-analysis. the signal explained 2% of pr interval variability in african americans (beta = 5.1 msec per minor allele,95% ci = 4.1-6.1,p = 3×10-23). this snp was also associated with pr interval (beta = 2.4 msec per minor allele,95% ci = 1.8-3.0,p = 3×10-16) in individuals of european ancestry (n = 14,042),but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). further meta-analysis of the four cohorts identified genome-wide significant associations with snps in scn10a (rs6798015),meis1 (rs10865355),and tbx5 (rs7312625) that were highly correlated with snps identified in european and asian gwa studies. african ancestry was associated with increased pr duration (13.3 msec,p = 0.009) in one but not the other three cohorts. our findings demonstrate the relevance of common variants to african americans at four loci previously associated with pr interval in european and asian samples and identify an association signal at one of these loci that is more strongly associated with pr interval in african americans than in europeans.
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آدرس
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department of cardiology,faculty of medicine,lund university,lund,sweden,program for medical and population genetics,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, section of cardiovascular medicine,boston university school of medicine,boston,ma,united states,national heart,lung and blood institute's framingham heart study,framingham,ma, United States, program for medical and population genetics,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, program for medical and population genetics,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, epidemiological cardiology center (epicare),department of epidemiology and prevention,wake forest university school of medicine,winston-salem,nc, United States, department of medicine,division of cardiovascular disease,university of mississippi medical center,jackson heart study,jackson,ms, United States, department of biostatistics,school of public health,university of washington,seattle,wa, United States, medical clinic 2 (cardiology),johannes-gutenberg university,mainz, Germany, division of preventive medicine,brigham and women's hospital,boston,ma,united states,cardiovascular research center,massachusetts general hospital and harvard medical school,boston,ma, United States, division of cardiology,department of medicine,university of washington,seattle,wa, United States, pediatrics,case western reserve university,cleveland,oh, United States, institute of human genetics,klinikum rechts der isar der technischen,universität münchen,münchen,germany,institute of human genetics,helmholtz centrum münchen,neuherberg, Germany, institute of medical informatics,biometry,and epidemiology and department of medicine i,university hospital grosshadern,ludwig-maximilians-universität,munich,germany,institute of epidemiology,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, diabetes center,university of california san francisco,san francisco,ca, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, department of epidemiology and prevention,division of public health sciences,wake forest university,winston-salem,nc, United States, department of epidemiology,graduate school of public health,university of pittsburgh,pittsburgh,pa, United States, national institute on aging,national institute on aging/nih-intramural research program,nih biomedical research center,baltimore,md, United States, national institute on aging,national institute on aging/nih-intramural research program,nih biomedical research center,baltimore,md, United States, division of cardiovascular medicine,university of pennsylvania,philadelphia,pa, United States, cardiovascular research center,massachusetts general hospital and harvard medical school,boston,ma,united states,center for human genetic research,massachusetts general hospital and harvard medical school,boston,ma, United States, division of cardiovascular sciences,national heart,lung,and blood institute,national institutes of health,bethesda,md, United States, program for medical and population genetics,broad institute of harvard and massachusetts institute of technology,cambridge,ma,united states,cardiovascular research center,massachusetts general hospital and harvard medical school,boston,ma,united states,center for human genetic research,massachusetts general hospital and harvard medical school,boston,ma, United States, section of cardiovascular medicine,boston university school of medicine,boston,ma,united states,national heart,lung and blood institute's framingham heart study,framingham,ma,united states,department of epidemiology,school of public health,boston university,massachusetts,united states,division of preventive medicine,boston university school of medicine,boston,ma,united states,whitaker cardiovascular institute,boston university school of medicine,boston,ma, United States, department of medicine,case school of medicine,cleveland,oh, United States, division of epidemiology and community health,school of public health,university of minnesota,minneapolis,mn, United States, department of epidemiology,university of washington,seattle,wa, United States, department of medicine,division of cardiovascular disease,university of mississippi medical center,jackson heart study,jackson,ms, United States
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Authors
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