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

Siew Kee Low, Atsushi Takahashi, Yusuke Ebana, Kouichi Ozaki, Ingrid E. Christophersen, Patrick T. Ellinor, Soichi Ogishima, Masayuki Yamamoto, Mamoru Satoh, Makoto Sasaki, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Keitaro Tanaka, Mariko Naito, Kenji Wakai, Hideo Tanaka, Tetsushi Furukawa, Michiaki Kubo, Kaoru ItoYoichiro Kamatani, Toshihiro Tanaka

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45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)953-958
Number of pages6
JournalNature Genetics
Volume49
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

ASJC Scopus subject areas

  • Genetics

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    Low, S. K., Takahashi, A., Ebana, Y., Ozaki, K., Christophersen, I. E., Ellinor, P. T., Ogishima, S., Yamamoto, M., Satoh, M., Sasaki, M., Yamaji, T., Iwasaki, M., Tsugane, S., Tanaka, K., Naito, M., Wakai, K., Tanaka, H., Furukawa, T., Kubo, M., ... Tanaka, T. (2017). Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nature Genetics, 49(6), 953-958. https://doi.org/10.1038/ng.3842