TY - JOUR
T1 - Transethnic Meta-Analysis of Genome-Wide Association Studies Identifies Three New Loci and Characterizes Population-Specific Differences for Coronary Artery Disease
AU - Matsunaga, Hiroshi
AU - Ito, Kaoru
AU - Akiyama, Masato
AU - Takahashi, Atsushi
AU - Koyama, Satoshi
AU - Nomura, Seitaro
AU - Ieki, Hirotaka
AU - Ozaki, Kouichi
AU - Onouchi, Yoshihiro
AU - Sakaue, Saori
AU - Suna, Shinichiro
AU - Ogishima, Soichi
AU - Yamamoto, Masayuki
AU - Hozawa, Atsushi
AU - Satoh, Mamoru
AU - Sasaki, Makoto
AU - Yamaji, Taiki
AU - Sawada, Norie
AU - Iwasaki, Motoki
AU - Tsugane, Shoichiro
AU - Tanaka, Keitaro
AU - Arisawa, Kokichi
AU - Ikezaki, Hiroaki
AU - Takashima, Naoyuki
AU - Naito, Mariko
AU - Wakai, Kenji
AU - Tanaka, Hideo
AU - Sakata, Yasuhiko
AU - Morita, Hiroyuki
AU - Sakata, Yasushi
AU - Matsuda, Koichi
AU - Murakami, Yoshinori
AU - Akazawa, Hiroshi
AU - Kubo, Michiaki
AU - Kamatani, Yoichiro
AU - Komuro, Issei
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Background: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD. Methods: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. Results: We identified 3 new loci on chromosome 1q21 (CTSS), 10q26 (WDR11-FGFR2), and 11q22 (RDX-FDX1). Quantitative trait locus analyses suggested the association of CTSS and RDX-FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. Conclusions: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.
AB - Background: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD. Methods: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. Results: We identified 3 new loci on chromosome 1q21 (CTSS), 10q26 (WDR11-FGFR2), and 11q22 (RDX-FDX1). Quantitative trait locus analyses suggested the association of CTSS and RDX-FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. Conclusions: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.
UR - http://www.scopus.com/inward/record.url?scp=85086681941&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086681941&partnerID=8YFLogxK
U2 - 10.1161/CIRCGEN.119.002670
DO - 10.1161/CIRCGEN.119.002670
M3 - Article
C2 - 32469254
AN - SCOPUS:85086681941
SN - 1942-325X
VL - 13
SP - E002670
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
IS - 3
ER -