EXOC3L2 rs597668 variant contributes to Alzheimer's disease susceptibility in Asian population.

Qing-Jian Wu,Hou-Wen Cheng,Ming-Feng Yang,Zi-Cui Cheng,Zi-Fei Li,Ti-Kun Fang,Cheng-Jun Yan,Shu-Yin Sun

doi:10.18632/oncotarget.15380

Qing-Jian Wu, Hou-Wen Cheng + Show 6 more

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https://doi.org/10.18632/oncotarget.15380

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Abstract

Recent genome-wide association studies have established the association between EXOC3L2 rs597668 variant and Alzheimer's disease (AD) in European population. However, recent studies reported inconsistent results in Asian population. Here, we performed a systematic review and meta-analysis to evaluate the impact of rs597668 on AD risk in Asian population using a total of 8686 samples including 2855 cases and 5831 controls. Meanwhile, we selected 17,008 AD cases and 37,154 controls in European population to evaluate the potential heterogeneity between East Asian and European populations. In East Asian population, we identified no potential heterogeneity with P=0.31 and I2 = 15.8%. By meta-analysis, we identified positive association between rs597668 and AD risk with P=0.023, OR=0.93, 95% CI 0.87-0.99. We further found significant heterogeneity in pooled Asian and European populations with P<0.0001 and I2 = 87.7%. The meta-analysis indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11. In summary, all these findings indicate that rs597668 C allele is a risk factor for AD in European population with OR=1.18 and P=2.49E-13. However the rs597668 C allele played a protective role in AD with OR=0.93 and P=0.023 in East Asian population.

Highlights

Alzheimer’s disease (AD) is the most common dementia in elderly [1,2,3]
In East Asian population, we identified no potential heterogeneity with P=0.31 and I2 = 15.8%
The meta-analysis indicated negative association with P=0.66, OR=0.97, 95% CI 0.85-1.11

Summary

Introduction

Alzheimer’s disease (AD) is the most common dementia in elderly [1,2,3]. In recent several years, largescale genome-wide association studies (GWAS) and generation sequencing analysis have identified a number of AD susceptibility genes including CLU [4,5,6,7,8], CR1 [9,10,11], BIN1 [12,13,14], PICALM [15,16,17,18], CD2AP [13, 19], CD33 [20,21], ABCA7 [7,8, 11, 13,14, 22], TREM2 [23,24], MS4A4/MS4A6E [25,26,27,28,29], EPHA1 [25,26,27,28,29], and EXOC3L2 [25,26,27,28,29,30].In these AD susceptibility genes above, a genetic variant rs597668 near EXOC3L2 was significantly associated with AD in European population withP=6.450E-09 [27]. Largescale genome-wide association studies (GWAS) and generation sequencing analysis have identified a number of AD susceptibility genes including CLU [4,5,6,7,8], CR1 [9,10,11], BIN1 [12,13,14], PICALM [15,16,17,18], CD2AP [13, 19], CD33 [20,21], ABCA7 [7,8, 11, 13,14, 22], TREM2 [23,24], MS4A4/MS4A6E [25,26,27,28,29], EPHA1 [25,26,27,28,29], and EXOC3L2 [25,26,27,28,29,30] In these AD susceptibility genes above, a genetic variant rs597668 near EXOC3L2 was significantly associated with AD in European population with. Both studies reported negative association between rs597668 and www.impactjournals.com/oncotarget

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