Ethnic similarities in genetic polymorphisms associated with atrial fibrillation: Far East Asian vs European populations

Myunghee Hong, Yusuke Ebana, Jaemin Shim, Eue Keun Choi, Hong Euy Lim, Inseok Hwang, Hee Tae Yu, Tae Hoon Kim, Jae Sun Uhm, Boyoung Joung, Seil Oh, Moon Hyoung Lee, Young Hoon Kim, Sun Ha Jee, Hui Nam Pak

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In European ancestry, 111 genetic loci were identified as associated with atrial fibrillation (AF). We explored the reproducibility of those single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) meta-analysis of Far East Asian populations. Methods: We performed a meta-analysis of the Korean AF network and Japanese AF data sets (9118 cases and 33 467 controls) by an inverse-variance fixed-effects model. We compared the results with 111 previously reported SNPs proven in Europeans after excluding 36 missing loci and a locus with a minor allelic frequency (MAF) < 0.01 in the European population. Results: Among remaining 74 loci, 29 loci were replicated at a P <.05, and 17 of those loci were newly found in the Far East Asian population: 3 loci with a P < 5×10−8 (METTL11B at 1q24, KCNN2 at 5q22 and LRMDA at 10q22), 4 loci at the threshold of the Bonferroni correction of P = 4.5 × 10−4 ~ 5×10−8 (KIF3C at 2p23, REEP3, NRBF2 at 10q21, SIRT1, MYPN at 10q21 and CFL2 at 14q13) and 10 SNPs with a P =.05 ~ 4.5 × 10−4. Among 18 AF loci with a MAF< 0.01 in the Far East Asian populations, 2 loci (GATA4 at 8q23 and SGCG at 13q12) were replicated after a fine mapping. Twenty-seven AF loci, including a locus, which had a sufficient sample size to get a power of over 80% (with a type 1 error α = 4.5 × 10−4), were not replicated in the Far East Asian populations. Conclusions: We newly replicated 19 AF-associated genetic loci in the European descent among the Far East Asian populations. It highlights the extensive sharing of AF genetic risks across Far East Asian populations.

Original languageEnglish
JournalEuropean Journal of Clinical Investigation
DOIs
Publication statusAccepted/In press - 2021

Bibliographical note

Funding Information:
This work was supported by grants [HI18C0070 to H‐NP] and [HI19C0114 to H‐NP] from the Ministry of Health and Welfare, grants [NRF‐2020R1A2B01001695 to H‐NP] and [NRF‐2019R1I1A1A01041440 to MH] from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education

Publisher Copyright:
© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry

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