Metrics details Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS) genetic risk variants reported to date explain only a small fraction of heritability To identify novel susceptibility variants for CAD and confirm those previously identified in European population GWAS and a replication study were performed in the Koreans and Japanese we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs imputation was performed based on 1000 Genome JPT+CHB and 5.1 million SNPs were retained CAD association was replicated for three GWAS-identified loci (1p13.3/SORT1 (rs599839) SNP rs3782889 showed a strong association (combined P=3.95 × 10−14) although the association of SNP rs3782889 doesn’t remain statistically significant after adjusting for SNP rs11066015 (proxy SNP with BRAP (r2=1)) But new possible CAD-associated variant was observed for rs9508025 (FLT1) even though its statistical significance did marginally reach at the genome-wide a significance level (combined P=6.07 × 10−7) This study shows that three CAD susceptibility loci which were previously identified in European can be directly replicated in Koreans and also provides additional evidences implicating suggestive loci as risk variants for CAD in East Asian we conducted GWAS and a replication study to identify common CAD susceptibility loci and validate the previously reported loci using Affymetrix Genome-Wide Human SNP array 6.0 with 2293 CAD patients from Genomics Research in Cardiovascular Disease (GenRIC) and 4302 healthy controls from a large urban cohort the Korea Genome Epidemiology Study (KoGES) as Stage I replication was performed using 3052 cases and 4976 controls from the KItaNagoya Genome (King) study of Japan we found evidence for genetic variants that may be associated with CAD risk The study protocol was approved by the institutional review boards at Korea National Institute of Health and at each collaborating institute Informed consent was obtained from all participants a GWA scan (GWAS) was conducted with 2293 CAD patients from GenRIC working groups consisting with three teaching hospitals (Samsung Medical Center Seoul National University Hospital and Yonsei University College of Medicine) in Korea CAD was confirmed by standard coronary angiography stable angina (41%) and unstable angina (28%) were classified as CAD subjects The diagnosis of myocardial infarction was based on typical chest pain with a duration >30 min on characteristic electrocardiographic patterns of acute myocardial infarction and on elevated creatine kinase-MB and troponin I levels Subjects with familial hypercholesterolemia end-stage renal disease and congenital heart disease were excluded Genetic variants in samples from 2293 cases and 4302 controls were genotyped using the Affymetrix Genome-Wide Human SNP array 6.0. The BirdSeed (http://www.broadinstitute.org/mpg/birdsuite/birdseed.html) genotyping algorithm was used for genotype calling. The PLINK program (Ver. 1.06) and R statistics (http://www.r-project.org/) (Ver 2.10.1) were used for quality control procedures Samples with any of the following were removed: (i) gender inconsistencies (n=23 in cases (iii) outliers in a heterozygosity plot (n=41 in cases (iv) cryptic first-degree relative>0.8 (n=9 in cases or (v) outliers in a multidimensional scaling plot (n=3 in cases Samples with a history of cancer and CAD were also excluded (in controls duplications and cryptic first-degree relative sibling pairs genome-wide average IBS values were calculated for each pair of individuals in the present GWA case−control data set using pruned SNPs (51 195 SNPs in 2123 cases and 74 965 SNPs in 3703 controls) individuals who shared a too high degree of IBS were excluded To evaluate differences in population structure an multidimensional scaling calculation was performed using pruned SNPs SNPs were filtered if: (1) the call rate was <95% (n=92 682 in cases (2) the minor allele frequency (MAF) was <1% (n=83 902 in cases (3) the difference between case and control was missing (P<5 × 10−5) (41 142 SNPs in cases and controls) (4) differential genotype calling rate between the cases and controls (case missing rate >1% or control missing rate >1% and (5) significant deviation from Hardy-Weinberg equilibrium (HWE P⩽1 × 10−6) were also filtered 521 786 autosomal SNPs in 2123 cases and in 3591 controls remained for association analysis For replication, fourteen significant candidate loci in GWAS scan were examined for replication using 3052 cases and 4976 controls using TaqMan SNP genotyping assay (Supplementary Figure S1) The minimum genotyping success rate in replication study was 0.993 and Hardy–Weinberg equilibrium test P-value showed >0.05 in control group suggesting no fault in genotyping procedure We selected the SNPs if they were implicated in previous GWAS studies and reported from the National Human Genome Research Institute catalog (http://www.genome.gov/gwastudies) We included SNPs only if they have assigned reference allele and estimated OR or β-coefficient and 95% confidence interval (CI) All SNPs successfully imputed were used (imputation QC R2<0.3) Regional plots of the –log P-values for three replicated loci (a–c) Results (–log P) are shown for the association of directly genotyped and imputed SNPs for a 1-Mb region centered on SNP reported in previous genome-wide association studies (GWAS) (diamond) Genotyped SNPs are represented as square and imputed SNPs are marked by circle SNPs for replication were selected on the basis of the following criteria among the 521,786 SNPs directly genotyped that had passed QC procedure: SNPs (a) with an MAF of >5% (b) with very clear genotyping clusters (c) with P-value of <5 × 10−4 and (d) not in strong LD (R2<0.5) with any of the GWAS-identified risk variants when multiple SNPs showed LD within 100kb (R2>0.2) the SNP with the lowest P-value was selected for replication SNPs with MAF of between 1% and 5% is ∼50 000 and fifty SNPs (0.1%) have the P-value of <5 × 10−4 these SNPs didn’t meet other replication criteria we did performed logistic regression by adjusting age and gender The combined analysis was performed by fixed effects and weighted numbers of samples and combined P-values and ORs were calculated using the Mantel-Haenszel test in RMETA in the R package as we found CAD association of variant previously identified on 12q24 in the Japanese we examined independent test at chromosomal position 12q24.11 using SNP (rs11066011) as a proxy of BRAP Manhattan plots for genome-wide association studies (GWAS) of coronary artery disease (CAD) in the Koreans The horizontal solid red line indicates the preset threshold of P=5 × 10−8 After SNP quality control and mapping of genomic positions to build37, a total of 5 125 961 SNPs for 5714 samples were retained as input genotype data for imputation. Among previously identified CAD loci, imputed SNPs for 9p21.3 and 12q24 loci were satisfied the P-value of GWAS significance (5 × 10−8) (Supplementary Table S7) the associations of other SNPs were not significant in the study possibly owing to the limited power of current study For the established risk locus within TCF21 (rs12190287) we could not evaluate the same SNPs as reported because they were not genotyped or successfully imputed (imputation QC R2<0.3) capturing TCF21 for rs12190287 (R2=0.24 in CHB+JTP; R2=0.35 in CEU) and rs9457925 in replacement for LPA rs3798220 (R2=0.31 in CHB+JPT; R2=none) and rs2246833 in replacement for LIPA rs1412444 (R2=0.86 in CHB+JPT; R2=1.00 in CEU) on the basis of 1000 genomes pilot1 data Even though the association of rs3782889 (in MYL2) was identified with Korean GWAS and directly replicated in the Japanese it couldn’t escape the possibility that the potential presence of LD block around MYL2 is not independent of the one around BRAP previously identified in Japanese The multi-ethnic studies will be required to contribute a better understanding of genetic architecture of CAD and pathogenesis we have confirmed four SNPs in three loci of CAD that were initially identified in Europeans provided additional evidence suggesting association in the risk of CAD susceptibility variants Future studies including fine mapping study functional assay and replication study with large sample sizes from diverse ethnic populations need to validate our results Global and regional burden of disease and risk factors 2001: systematic analysis of population health data Molecular genetics of coronary artery disease Genetic susceptibility to death from coronary heart disease in a study of twins Thirty-five common variants for coronary artery disease: the fruits of much collaborative labour Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease Design of the Coronary ARtery DIsease Genome-Wide Replication And 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progress report Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians Genome-wide association study identifies eight loci associated with blood pressure Genome-wide association study of blood pressure and hypertension Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits clinical and population relevance of 95 loci for blood lipids Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease Association of SNP rs17465637 on chromosome 1q41 and rs599839 on 1p13.3 with myocardial infarction in an American caucasian population Factors of risk in the development of coronary heart disease--six year follow-up experience Correcting "winner's curse" in odds ratios from genomewide association findings for major complex human diseases Download references We thank all participants and investigators of the GenRIC study and the Korea Genome Epidemiology Study (KoGES) This work was supported by grants from the Korea Centers for Disease Control and Prevention (4845-301) an intramural grant from the Korea National Institute of Health (2011-N73007-00 Dong-Jik Shin and Kyung Woo Park: These authors contributed equally to this work Jeong Euy Park and Jong-Young Lee: These authors jointly directed this work Sungkyunkwan University School of Medicine Interdisciplinary Program in Bioinformatics Division of Pulmonary and Critical Care Medicine Osong Health Technology Administration complex The authors declare no conflict of interest Supplementary Information accompanies the paper on Journal of Human Genetics website Download citation Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Please view the main text area of the page by skipping the main menu. The page may not be displayed properly if the JavaScript is deactivated on your browser Today's print edition Home Delivery Nagoya is seeing a growing number of "tsukinists," a term coined for those who commute to work by bicycle pointing to the public's higher awareness of environmental and personal health issues The city has also shown its support for tsukinists — the word is based on the word "tsukin" (commute) — by ensuring there are sufficient bicycle lanes in the city.googletag.cmd.push(function() { googletag.display('div-gpt-ad-1499653692894-0'); }); companies have done little to support the trend so whether Nagoya's bicycle commuting boom will continue is an open question In a time of both misinformation and too much information quality journalism is more crucial than ever.By subscribing Your subscription plan doesn't allow commenting. To learn more see our FAQ Sponsored contents planned and edited by JT Media Enterprise Division VISITING STUDENTS: Middle school students from Kitanagoya City and representatives from their school visited the Guam Visitors Bureau on Monday The students sat through a short presentation about Guam from the GVB team asked questions and learned the Boonie Stomp dance during their courtesy visit GVB Japan Marketing Manager Brian Borja and Marketing Coordinator Karida Brennan met the Japanese school officials and students from Kitanagoya City Photo courtesy of the Guam Visitors Bureau Poll results are published every Monday in The Guam Daily Post Your browser is out of date and potentially vulnerable to security risks.We recommend switching to one of the following browsers: University of Guam students and faculty are leveraging international academic conferences to foster economic innovation and workforce development positioning the island as a hub for what School of Business and Public Administration Dean Roseann Jones Saturday’s Mad Collab Block Party in Hagåtña brought together more than 70 local businesses and artists in celebration with hundreds of attendees It was all about the wonders of Artificial Intelligence in the palm of your hand All of the latest features in Samsung's Galaxy AI were showcased at a GTA-sponsored event Thursday Japanese version