与心房颤动相关的遗传多态性的种族相似性：远东东亚与欧洲人群。

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

机构信息

Division of Cardiology, Department of Internal Medicine, Yonsei University Health System, Seoul, Korea.

Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.

出版信息

Eur J Clin Invest. 2021 Sep;51(9):e13584. doi: 10.1111/eci.13584. Epub 2021 May 14.

DOI:10.1111/eci.13584

PMID:33990960

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 (METTL11B at 1q24, KCNN2 at 5q22 and LRMDA at 10q22), 4 loci at the threshold of the Bonferroni correction of P = 4.5 × 10 ~ 5×10 (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 . 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 ), 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.

摘要

背景

在欧洲血统中，有 111 个遗传位点被确定与心房颤动（AF）相关。我们通过全基因组关联研究（GWAS）荟萃分析探索了这些单核苷酸多态性（SNP）在东亚人群中的可重复性。

方法

我们通过逆方差固定效应模型对韩国 AF 网络和日本 AF 数据集（8118 例病例和 33467 例对照）进行荟萃分析。我们将结果与在欧洲人群中经排除 36 个缺失位点和一个等位基因频率（MAF）<0.01 的位点后证实的 111 个先前报告的 SNP 进行比较。

结果

在其余的 74 个位点中，有 29 个在 P<0.05 时得到复制，其中 17 个在东亚人群中被新发现：3 个位点 P<5×10（METTL11B 在 1q24，KCNN2 在 5q22，LRMDA 在 10q22），4 个位点在 Bonferroni 校正的 P=4.5×10~~5×10 边界（KIF3C 在 2p23，REEP3，NRBF2 在 10q21，SIRT1，MYPN 在 10q21 和 CFL2 在 14q13），还有 10 个 SNP 的 P=0.05~~4.5×10。在东亚人群中 MAF<0.01 的 18 个 AF 位点中，有 2 个位点（GATA4 在 8q23 和 SGCG 在 13q12）在精细映射后得到复制。在东亚人群中，有 27 个 AF 位点，包括一个具有超过 80%的检测效能（α=4.5×10）的足够样本量的位点，未得到复制。