TY - JOUR
T1 - Identification of six new genetic loci associated with atrial fibrillation in the Japanese population
AU - Low, Siew Kee
AU - Takahashi, Atsushi
AU - Ebana, Yusuke
AU - Ozaki, Kouichi
AU - Christophersen, Ingrid E.
AU - Ellinor, Patrick T.
AU - Ogishima, Soichi
AU - Yamamoto, Masayuki
AU - Satoh, Mamoru
AU - Sasaki, Makoto
AU - Yamaji, Taiki
AU - Iwasaki, Motoki
AU - Tsugane, Shoichiro
AU - Tanaka, Keitaro
AU - Naito, Mariko
AU - Wakai, Kenji
AU - Tanaka, Hideo
AU - Furukawa, Tetsushi
AU - Kubo, Michiaki
AU - Ito, Kaoru
AU - Kamatani, Yoichiro
AU - Tanaka, Toshihiro
N1 - Funding Information:
This study was in part supported by the Naito Foundation Natural Science Scholarship to T.T. This study was also funded by the BioBank Japan project and the Tohoku Medical Megabank project, which is supported by the Ministry of Education, Culture, Sports, Sciences and Technology Japan and the Japan Agency for Medical Research and Development. The JPHC Study has been supported by the National Cancer Research and Development Fund since 2010 and was supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan from 1989 to 2010. The J-MICC Study was supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (17015018) and Innovative Areas (221S0001) and the JSPS KAKENHI Grant (16H06277) from the Japan Ministry of Education, Science, Sports, Culture and Technology. The following research institutions participated in the study: Chiba Cancer Center, University of Shizuoka, Nagoya City University, Aichi Cancer Center, Nagoya University, Shiga University of Medical Science, Kyoto Prefectural University of Medicine, University of Tokushima, Kyushu University, Saga University and Kagoshima University. This work was supported by grants from the US National Institutes of Health to P.T.E. (1RO1HL092577, R01HL128914, K24HL105780). P.T.E. is also supported by an Established Investigator Award from the American Heart Association (13EIA14220013) and by the Fondation Leducq (14CVD01).
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To investigate genetic loci associated with atrial fibrillation in the Japanese population, we performed a genome-wide association study (GWAS) that included 8,180 atrial fibrillation cases and 28,612 controls with follow-up in an additional 3,120 cases and 125,064 controls. We replicated previously reported loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2, NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated with atrial fibrillation in the Japanese population after comparing our data to those from individuals of European ancestry, suggesting that there might be different genetic factors affecting susceptibility across ancestry groups. Our study discovered variants in the HAND2, KCND3 and NEBL genes, which are relevant to atrial fibrillation susceptibility. The involvement of PPFIA4 and SH3PXD2A in axon guidance also suggested a role in disease pathogenesis. Our findings may contribute to a better understanding of atrial fibrillation susceptibility and pathogenesis.
AB - Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To investigate genetic loci associated with atrial fibrillation in the Japanese population, we performed a genome-wide association study (GWAS) that included 8,180 atrial fibrillation cases and 28,612 controls with follow-up in an additional 3,120 cases and 125,064 controls. We replicated previously reported loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2, NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated with atrial fibrillation in the Japanese population after comparing our data to those from individuals of European ancestry, suggesting that there might be different genetic factors affecting susceptibility across ancestry groups. Our study discovered variants in the HAND2, KCND3 and NEBL genes, which are relevant to atrial fibrillation susceptibility. The involvement of PPFIA4 and SH3PXD2A in axon guidance also suggested a role in disease pathogenesis. Our findings may contribute to a better understanding of atrial fibrillation susceptibility and pathogenesis.
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U2 - 10.1038/ng.3842
DO - 10.1038/ng.3842
M3 - Article
C2 - 28416822
AN - SCOPUS:85017499300
SN - 1061-4036
VL - 49
SP - 953
EP - 958
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -