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An Integrated Meta-Analysis of Two Variants in HOXA1/HOXB1 and Their Effect on the Risk of Autism Spectrum Disorders

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  • Ran-Ran Song
  • Li Zou
  • Rong Zhong
  • Xia-Wen Zheng
  • Bei-Bei Zhu
  • Wei Chen
  • Li Liu
  • Xiao-Ping Miao

Abstract

Background: HOXA1 and HOXB1 have been strongly posed as candidate genes for autism spectrum disorders (ASD) given their important role in the development of hindbrain. The A218G (rs10951154) in HOXA1 and the insertion variant in HOXB1 (nINS/INS, rs72338773) were of special interest for ASD but with inconclusive results. Thus, we conducted a meta-analysis integrating case-control and transmission/disequilibrium test (TDT) studies to clearly discern the effect of these two variants in ASD. Methods and Findings: Multiple electronic databases were searched to identify studies assessing the A218G and/or nINS/INS variant in ASD. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. A total of 10 and 7 reports were found to be eligible for meta-analyses of A218G and nINS/INS variant, respectively. In overall meta-analysis, the pooled OR for the 218G allele and the INS allele was 0.97 (95% CI = 0.76-1.25, Pheterogeneity = 0.029) and 1.14 (95% CI = 0.97-1.33, Pheterogeneity = 0.269), respectively. No significant association was also identified between these two variants and ASD risk in stratified analysis. Further, cumulative meta-analysis in chronologic order showed the inclination toward null-significant association for both variants with continual adding studies. Additionally, although the between-study heterogeneity regarding the A218G is not explained by study design, ethnicity, and sample size, the sensitive analysis indicated the stability of the result. Conclusions: This meta-analysis suggests the HOXA1 A218G and HOXB1 nINS/INS variants may not contribute significantly to ASD risk.

Suggested Citation

  • Ran-Ran Song & Li Zou & Rong Zhong & Xia-Wen Zheng & Bei-Bei Zhu & Wei Chen & Li Liu & Xiao-Ping Miao, 2011. "An Integrated Meta-Analysis of Two Variants in HOXA1/HOXB1 and Their Effect on the Risk of Autism Spectrum Disorders," PLOS ONE, Public Library of Science, vol. 6(9), pages 1-9, September.
    • Handle: RePEc:plo:pone00:0025603
    DOI: 10.1371/journal.pone.0025603
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    References listed on IDEAS

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    1. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
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    1. Zhenling Wang & Li Zou & Rong Zhong & Beibei Zhu & Wei Chen & Na Shen & Juntao Ke & Jiao Lou & Ranran Song & Xiao-Ping Miao, 2013. "Associations between Two Genetic Variants in NKX2-5 and Risk of Congenital Heart Disease in Chinese Population: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-6, August.

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