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RESEARCH PRODUCT
Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium
Kenneth RiceKaisa SilanderKaisa SilanderNicholas L. SmithNicholas L. SmithCharles C. WhiteBrendan M. BuckleyJarmo VirtamoKuulasmaa KariThomas LumleyThomas LumleyJ. Wouter JukemaDaniel I. ChasmanVilmundur GudnasonMarcello Ricardo Paulista MarkusEric BoerwinkleEric BoerwinkleAlbert HofmanAlanna C. MorrisonRamachandran S. VasanFernando RivadeneiraStephen B. KritchevskyGerardo HeissDaniel LevyHenry VölzkeKent D. TaylorBruce M. PsatyJuha KarvanenJuha KarvanenDominique ArveilerGudny EiriksdottirJingzhong DingEric B. RimmOscar H. FrancoYongmei LiuPaul M. RidkerTamara B. HarrisPhillippe AmouyelAbbas DehghanStefan BlankenbergL. Adrienne CupplesP J WagnerP J WagnerFrank KeeNora FranceschiniMajken K. JensenCara L. CartySerkalem DemissieLenore J. LaunerDavid J. StottVeikko SalomaaAlun EvansYing A. WangYing A. WangAaron R. FolsomJean FerrièresJoshua C. BisPierre DucimetièreJerome I. RotterMarcus DörrEmelia J. BenjaminPer-gunnar WiklundDavid S. SiscovickCynthia J. GirmanCynthia J. GirmanStella TrompetSusan R. HeckbertSusan R. HeckbertUwe VölkerPeter KraftAndré G. UitterlindenIan FordKurt LohmanLynda M. RoseAlbert V. SmithChristopher J. O'donnellsubject
Male0301 basic medicineOncologyPREDICTIONMyocardial Infarctionlcsh:MedicineGenome-wide association studyCoronary Artery DiseaseCardiovascular MedicineSUSCEPTIBILITY030204 cardiovascular system & hematologyCardiovascularBioinformaticsincident myocardial infarctionCohort StudiesCoronary artery diseaseMathematical and Statistical Techniques0302 clinical medicineDESIGNMedicine and Health Sciences2.1 Biological and endogenous factorsProspective StudiesMyocardial infarctionAetiologyCooperative Behaviorlcsh:ScienceProspective cohort studyRISKscreening and diagnosisMultidisciplinaryResearch Support Non-U.S. Gov'tSingle NucleotideGenomicsMiddle Aged3. Good healthMultidisciplinary SciencesDetectionCHROMOSOME 9P21Heart DiseaseResearch DesignCardiovascular DiseasesCARDIOVASCULAR-DISEASEPhysical SciencesScience & Technology - Other TopicsFemaleStatistics (Mathematics)4.2 Evaluation of markers and technologiesResearch ArticleCohort studymedicine.medical_specialtyGeneral Science & TechnologyCardiologySingle-nucleotide polymorphismResearch and Analysis MethodsGenome ComplexityPolymorphism Single Nucleotide03 medical and health sciencescoronary hearth diseaseInternal medicineMD MultidisciplinaryGenome-Wide Association StudiesGeneticsJournal ArticlemedicineHumansSNPGenetic Predisposition to DiseasePolymorphismStatistical MethodsHeart Disease - Coronary Heart DiseaseMETAANALYSISAgedGenetic associationta112Science & Technologybusiness.industryPreventionlcsh:RHuman GenomeBiology and Life SciencesComputational BiologyHuman GeneticsGenome AnalysisROTTERDAMmedicine.diseaseIntronsGood Health and Well Being030104 developmental biologyGenetic LociGenetics of Diseaselcsh:Q3111 BiomedicinebusinessMathematicsMeta-AnalysisGenome-Wide Association Studydescription
Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10−6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10−3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10−9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10−3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders. peerReviewed
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-03-07 | PLOS ONE |