title: Genetics of Coronary Artery Disease in Taiwan: A Cardiometabochip Study by the Taichi Consortium.
abstract: By means of a combination of genome-wide and follow-up studies, recent large-scale association studies of populations of European descent have now identified over 46 loci associated with coronary artery disease (CAD). As part of the TAICHI Consortium, we have collected and genotyped 8556 subjects from Taiwan, comprising 5423 controls and 3133 cases with coronary artery disease, for 9087 CAD SNPs using the CardioMetaboChip. We applied penalized logistic regression to ascertain the top SNPs that contribute together to CAD susceptibility in Taiwan. We observed that the 9p21 locus contributes to CAD at the level of genome-wide significance (rs1537372, with the presence of C, the major allele, the effect estimate is -0.216, standard error 0.033, p value 5.8x10-10). In contrast to a previous report, we propose that the 9p21 locus is a single genetic contribution to CAD in Taiwan because: 1) the penalized logistic regression and the follow-up conditional analysis suggested that rs1537372 accounts for all of the CAD association in 9p21, and 2) the high linkage disequilibrium observed for all associated SNPs in 9p21. We also observed evidence for the following loci at a false discovery rate >5%: SH2B3, ADAMTS7, PHACTR1, GGCX, HTRA1, COL4A1, and LARP6-LRRC49. We also took advantage of the fact that penalized methods are an efficient approach to search for gene-by-gene interactions, and observed that two-way interactions between the PHACTR1 and ADAMTS7 loci and between the SH2B3 and COL4A1 loci contribute to CAD risk. Both the similarities and differences between the significance of these loci when compared with significance of loci in studies of populations of European descent underscore the fact that further genetic association of studies in additional populations will provide clues to identify the genetic architecture of CAD across all populations worldwide.
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.affiliation: Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: I-T
authors.initials: IT
authors.lastname: Lee
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National University College of Medicine, Taipei, Taiwan.
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Juang
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and Department of Pediatrics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National University College of Medicine, Taipei, Taiwan.
authors.forename: Tzung-Dau
authors.initials: TD
authors.lastname: Wang
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and Department of Pediatrics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Kim
authors.affiliation: Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wen-Jane
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.affiliation: Institute of Population Health Sciences, Division of Biostatistics and Bioinformatics, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.affiliation: Institute of Population Health Sciences, Division of Biostatistics and Bioinformatics, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Division of Endocrine and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Chao A
authors.initials: CA
authors.lastname: Hsiung
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and Department of Pediatrics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wayne H-H
authors.initials: WH
authors.lastname: Sheu
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and Department of Pediatrics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and Department of Pediatrics, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan