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Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in european ancestry individuals
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نویسنده
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arking d.e. ,junttila m.j. ,goyette p. ,huertas-vazquez a. ,eijgelsheim m. ,blom m.t. ,newton-cheh c. ,reinier k. ,teodorescu c. ,uy-evanado a. ,carter-monroe n. ,kaikkonen k.s. ,kortelainen m.-l. ,boucher g. ,lagacé c. ,moes a. ,zhao x. ,kolodgie f. ,rivadeneira f. ,hofman a. ,witteman j.c.m. ,uitterlinden a.g. ,marsman r.f. ,pazoki r. ,bardai a. ,koster r.w. ,dehghan a. ,hwang s.-j. ,bhatnagar p. ,post w. ,hilton g. ,prineas r.j. ,li m. ,köttgen a. ,ehret g. ,boerwinkle e. ,coresh j. ,kao w.h.l. ,psaty b.m. ,tomaselli g.f. ,sotoodehnia n. ,siscovick d.s. ,burke g.l. ,marbán e. ,spooner p.m. ,cupples l.a. ,jui j. ,gunson k. ,kesäniemi y.a. ,wilde a.a.m. ,tardif j.-c. ,o'donnell c.j. ,bezzina c.r. ,virmani r. ,stricker b.h.c.h. ,tan h.l. ,albert c.m. ,chakravarti a. ,rioux j.d. ,huikuri h.v. ,chugh s.s.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 6
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چکیده
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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). © 2011 arking et al. this is an open-access article distributed under the terms of the creative commons attribution license,which permits unrestricted use,distribution,and reproduction in any medium,provided the original author and source are credited.
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آدرس
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mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md, United States, institute of clinical medicine,department of internal medicine,university of oulu,oulu,finland,division of cardiology,miller school of medicine,university of miami,miami,fl, United States, montreal heart institute,the université de montréal,montreal,qc, Canada, the heart institute,cedars-sinai medical center,los angeles,ca, United States, department of epidemiology,erasmus mc,rotterdam, Netherlands, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, center for human genetic research,massachusetts general hospital,boston,ma,united states,cardiology division,massachusetts general hospital,boston,ma,united states,framingham heart study,national heart,lung,and blood institute,national institutes of health,framingham,ma, United States, the heart institute,cedars-sinai medical center,los angeles,ca, United States, the heart institute,cedars-sinai medical center,los angeles,ca, United States, the heart institute,cedars-sinai medical center,los angeles,ca, United States, cvpath institute,gaithersburg,md, United States, institute of clinical medicine,department of internal medicine,university of oulu,oulu, Finland, institute of clinical medicine,department of internal medicine,university of oulu,oulu, Finland, montreal heart institute,the université de montréal,montreal,qc, Canada, montreal heart institute,the université de montréal,montreal,qc, Canada, mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md, United States, cvpath institute,gaithersburg,md, United States, cvpath institute,gaithersburg,md, United States, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ncha),netherlands genomic initiative (ngi),rotterdam, Netherlands, department of epidemiology,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ncha),netherlands genomic initiative (ngi),rotterdam, Netherlands, department of epidemiology,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ncha),netherlands genomic initiative (ngi),rotterdam, Netherlands, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ncha),netherlands genomic initiative (ngi),rotterdam, Netherlands, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, department of epidemiology,erasmus mc,rotterdam, Netherlands, framingham heart study,national heart,lung,and blood institute,national institutes of health,framingham,ma, United States, mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md, United States, division of cardiology,department of medicine,johns hopkins university school of medicine,baltimore,md, United States, mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md, United States, division of public health sciences,wake forest university school of medicine,winston-salem,nc, United States, department of epidemiology,johns hopkins university,baltimore,md, United States, department of epidemiology,johns hopkins university,baltimore,md, United States, mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md,united states,cardiology,department of medicine,geneva university hospital,geneva, Switzerland, university of texas health science center at houston,houston,tx, United States, department of epidemiology,johns hopkins university,baltimore,md,united states,departments of medicine and biostatistics,johns hopkins university,baltimore,md, United States, department of epidemiology,johns hopkins university,baltimore,md, United States, cardiovascular health research unit,departments of medicine and epidemiology,university of washington,seattle,wa,united states,group health research institute,group health cooperative,seattle,wa, United States, division of cardiology,department of medicine,johns hopkins university school of medicine,baltimore,md, United States, cardiovascular health research unit,division of cardiology,department of medicine,university of washington,seattle,wa, United States, cardiovascular health research unit,departments of medicine and epidemiology,university of washington,seattle,wa, United States, division of public health sciences,wake forest university school of medicine,winston-salem,nc, United States, the heart institute,cedars-sinai medical center,los angeles,ca, United States, division of cardiology,department of medicine,johns hopkins university school of medicine,baltimore,md, United States, framingham heart study,national heart,lung,and blood institute,national institutes of health,framingham,ma,united states,department of biostatistics,boston university school of public health,boston,ma, United States, department of emergency medicine,oregon health and science university,portland,or, United States, department of pathology,oregon health and science university,portland,or, United States, institute of clinical medicine,department of internal medicine,university of oulu,oulu,finland,biocenter oulu,university of oulu,oulu, Finland, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, montreal heart institute,the université de montréal,montreal,qc, Canada, framingham heart study,national heart,lung,and blood institute,national institutes of health,framingham,ma,united states,national heart,lung,and blood institute,bethesda,md, United States, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, cvpath institute,gaithersburg,md, United States, department of epidemiology,erasmus mc,rotterdam,netherlands,department of internal medicine,erasmus mc,rotterdam,netherlands,netherlands consortium for healthy aging (ncha),netherlands genomic initiative (ngi),rotterdam,netherlands,department of medical informatics,erasmus mc,rotterdam,netherlands,inspectorate of health care,the hague, Netherlands, heart failure research center,department of clinical and experimental cardiology,academic medical center,university of amsterdam,amsterdam, Netherlands, center for arrhythmia prevention,division of preventive medicine,cardiovascular division,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, mckusick-nathans institute of genetic medicine,johns hopkins university school of medicine,baltimore,md, United States, montreal heart institute,the université de montréal,montreal,qc, Canada, institute of clinical medicine,department of internal medicine,university of oulu,oulu, Finland, the heart institute,cedars-sinai medical center,los angeles,ca, United States
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Authors
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