Genomic Variants in NEURL, GJA1 and CUX2 Significantly Increase Genetic Susceptibility to Atrial Fibrillation

Pengxia Wang,Xiaojing Wang,Yufeng Huang,Qiuyun Chen,Bo Yang,Mugen Liu,Yanzong Yang,Yi Xiao,He Li,Feifei Chen,Yanxia Wu,Xin Tu,Pengyun Wang,Sisi Li,Xiang Cheng,Xiaoping Luo,Rongfeng Zhang,Qin Yang,Xiang Ren,Jingyu Liu,Yuhua Liao,Weixi Qin,Tie Ke,Chengqi Xu,Ying Liu,Qing Kenneth Wang

doi:10.1038/s41598-018-21611-7

Abstract

Atrial fibrillation (AF) is the most common arrhythmia. In 2014, two new meta-GWAS identified 5 AF loci, including the NEURL locus, GJA1 locus, CAND2 locus, and TBX5 locus in the European ancestry populations and the NEURL locus and CUX2 locus in a Japanese population. The TBX5 locus for AF was reported by us in 2013 in the Chinese population. Here we assessed the association between AF and SNPs in the NEURL, GJA1, CAND2 and CUX2 loci in the Chinese Han population. We carried out a large case-control association study with 1,164 AF patients and 1,460 controls. Significant allelic and genotypic associations were identified between NEURL variant rs6584555 and GJA1 variant rs13216675 and AF. Significant genotypic association was found between CUX2 SNP rs6490029 and AF. No association was found between CAND2 variant rs4642101 and AF, which may be due to an insufficient power of the sample size for rs4642101. Together with our previous findings, seven of fifteen AF loci (<50%) identified by GWAS in the European ancestry populations conferred susceptibility to AF in the Chinese population, and explained approximately 14.5% of AF heritability. On the other hand, two AF loci identified in the Japanese population were both replicated in the Chinese population.

Highlights

Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, P.R
We analyzed four genomic variants associated with Atrial fibrillation (AF) in either the European ancestry populations or the Japanese population for their association with AF in the Chinese Han population
The CAND2 locus was not replicated in the Chinese population (Tables 2 and 3), which may be due to an insufficient power of the sample size for this variant

Summary

Introduction

Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, P.R. In 2014, meta-GWAS in the European ancestry populations identified additional AF susceptibility variants, including NEURL SNPs rs12415501, CAND2 SNP rs4642101, GJA1 SNP rs13216675 and TBX5 SNP rs1050724817. We assessed association between AF with other meta-GWAS SNPs identified in European ancestry populations and the Japanese population, including SNP rs6584555 in NEURL, rs13216675 near GJA1, rs4642101 in CAND2 and rs6490029 in CUX2, in the Chinese GeneID population. We identified significant allelic and genotypic association between NEURL rs6584555 and GJA1 SNP rs13216675 and AF, significant genotypic association between CUX2 SNP rs6490029 and AF, but no association between CAND2 SNP rs4642101 and AF

Methods

Results

Conclusion