Reelin gene variants and risk of autism spectrum disorders: an integrated meta-analysis

Am J Med Genet B Neuropsychiatr Genet. 2014 Mar;165B(2):192-200. doi: 10.1002/ajmg.b.32222. Epub 2014 Jan 22.

Abstract

Autism spectrum disorder (ASD) is a severe neurological disorder with a high degree of heritability. Reelin gene (RELN), which plays a crucial role in the migration and positioning of neurons during brain development, has been strongly posed as a candidate gene for ASD. Genetic variants in RELN have been investigated as risk factors of ASD in numerous epidemiologic studies but with inconclusive results. To clearly discern the effects of RELN variants on ASD, the authors conducted a meta-analysis integrating case-control and transmission disequilibrium test (TDT) studies published through 2001 to 2013. Odds ratios (ORs) with 95% confidence intervals were used to estimate the associations between three RELN variants (rs736707, rs362691, and GGC repeat variant) and ASD. In overall meta-analysis, the summary ORs for rs736707, rs362691, and GGC repeat variant were 1.11 [95% confidence interval (CI): 0.80-1.54], 0.69 (95% CI: 0.56-0.86), and 1.09 (95% CI: 0.97-1.23), respectively. Besides, positive result was also obtained in subgroup of broadly-defined ASD for rs362691 (OR = 0.67, 95% CI: 0.52-0.86). Our meta-analysis revealed that the RELN rs362691, rather than rs736707 or GGC repeat variant, might contribute significantly to ASD risk.

Keywords: ASD; RELN gene; epidemiology; genetics; polymorphism.

Publication types

  • Meta-Analysis

MeSH terms

  • Cell Adhesion Molecules, Neuronal / genetics*
  • Child Development Disorders, Pervasive / genetics*
  • Extracellular Matrix Proteins / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Reelin Protein
  • Risk
  • Serine Endopeptidases / genetics*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • RELN protein, human
  • Serine Endopeptidases