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Analyzing Large-Scale Samples Confirms the Association Between the ABCA7 rs3764650 Polymorphism and Alzheimer’s Disease Susceptibility

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Abstract

Large-scale genome-wide association studies (GWAS) have revealed that the ABCA7 rs3764650 polymorphism (or its proxies, namely rs115550680, rs3752246, and rs4147929) is associated with Alzheimer’s disease (AD) susceptibility in individuals of Caucasian ancestry. The following studies have investigated this finding in Chinese (N = 633 and N = 1,224), Japanese (N = 1,735), Korean (N = 844), African American (N = 5,896), and Canadian (N = 1,104) populations. However, these studies reported a weak or negligible association. We hypothesized that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in individuals of Caucasian ancestry or the genetic heterogeneity of the rs3764650 polymorphism (or its proxies) in different populations. Here, we reevaluated the association between rs3764650 and AD using large-scale samples from 18 previous studies (N = 79,381—30,590 cases and 48,791 controls) by searching PubMed, AlzGene, and Google Scholar databases. Using allele, dominant, recessive, and additive models, we did not identify significant heterogeneity among the 18 studies. We observed a significant association between rs3764650 and AD using the allele (P = 1.76E − 26, odds ratio (OR) = 1.21, 95 % confidence interval (CI) 1.17–1.26), dominant (P = 4.00E − 04, OR = 1.17, 95 % CI 1.07–1.28), recessive (P = 3.00E − 03, OR = 1.43, 95 % CI 1.13–1.81), and additive models (P = 3.00E − 03, OR = 1.49, 95 % CI 1.16–1.91). Collectively, our analysis further supports previous findings that the ABCA7 rs3764650 polymorphism is associated with AD susceptibility. We believe that our findings will be very useful for future genetic studies on AD.

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Acknowledgments

This work was supported by funding from the National Nature Science Foundation of China (grant numbers 81300945, 31200934, 31301938, 31171219, 81271213, 81070878, 81271214, and 81261120404), the Natural Science Foundation of Guangdong Province, China (No. S2012010008222), and the Science and Technology Innovation Fund of Guangdong Medical College (No. STIF 201101).

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Authors and Affiliations

  1. Institute of Neurology, Guangdong Medical College, Zhanjiang, 524001, China

    Guiyou Liu, Guoda Ma & Keshen Li

  2. Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Xiqi Dao 32, Tianjin Airport Economic Area, Tianjin, 300308, China

    Guiyou Liu

  3. Department of Anesthesiology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

    Fujun Li

  4. Department of Neurology, The Forth Affiliated Hospital of Harbin Medical University, Harbin, China

    Shuyan Zhang & Hong Shang

  5. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

    Yongshuai Jiang & Mingzhi Liao

  6. Department of Neurology, The First Hospital of Harbin, Harbin, China

    Jiafeng Liu

  7. Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China

    Rennan Feng

  8. Department of Statistics, Rice University, Houston, TX, USA

    Liangcai Zhang

  9. Key Laboratory of Aging-Related Cardio-Cerebral Diseases of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China

    Bin Zhao & Keshen Li

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  1. Guiyou Liu
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Correspondence to Guiyou Liu or Keshen Li.

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Guiyou Liu, Fujun Li, and Shuyan Zhang contributed equally to this work.

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Liu, G., Li, F., Zhang, S. et al. Analyzing Large-Scale Samples Confirms the Association Between the ABCA7 rs3764650 Polymorphism and Alzheimer’s Disease Susceptibility. Mol Neurobiol 50, 757–764 (2014). https://doi.org/10.1007/s12035-014-8670-4

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