. 2017 Jun;49(6):953-958.

doi: 10.1038/ng.3842. Epub 2017 Apr 17.

Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

Siew-Kee Low^{1

2}, Atsushi Takahashi^{1

3}, Yusuke Ebana⁴, Kouichi Ozaki^{5

6}, Ingrid E Christophersen^{7

8

9}, Patrick T Ellinor⁷; AFGen Consortium; Soichi Ogishima¹⁰, Masayuki Yamamoto¹⁰, Mamoru Satoh¹¹, Makoto Sasaki¹¹, Taiki Yamaji¹², Motoki Iwasaki¹², Shoichiro Tsugane¹³, Keitaro Tanaka¹⁴, Mariko Naito¹⁵, Kenji Wakai¹⁵, Hideo Tanaka^{16

17}, Tetsushi Furukawa⁴, Michiaki Kubo¹⁸, Kaoru Ito⁵, Yoichiro Kamatani¹, Toshihiro Tanaka^{5

19}

Affiliations

¹ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
³ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
⁴ Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵ Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁶ Laboratory for Medical Genome Sciences, Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan.
⁷ Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
⁸ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁹ Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
¹⁰ Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
¹¹ Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
¹² Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
¹³ Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
¹⁴ Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
¹⁵ Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
¹⁷ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁸ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁹ Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.

PMID: 28416822
DOI: 10.1038/ng.3842

Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

Siew-Kee Low et al. Nat Genet. 2017 Jun.

. 2017 Jun;49(6):953-958.

doi: 10.1038/ng.3842. Epub 2017 Apr 17.

Authors

Affiliations

¹ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
² Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
³ Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan.
⁴ Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵ Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
⁶ Laboratory for Medical Genome Sciences, Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Japan.
⁷ Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
⁸ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁹ Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
¹⁰ Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
¹¹ Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
¹² Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
¹³ Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
¹⁴ Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga, Japan.
¹⁵ Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
¹⁷ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁸ RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁹ Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan.

PMID: 28416822
DOI: 10.1038/ng.3842

Abstract

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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Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

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Identification of six new genetic loci associated with atrial fibrillation in the Japanese population

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