SMN1 duplications contribute to sporadic amyotrophic lateral sclerosis susceptibility: evidence from a meta-analysis

J Neurol Sci. 2014 May 15;340(1-2):63-8. doi: 10.1016/j.jns.2014.02.026. Epub 2014 Feb 28.


Objective: To investigate the association between SMN1 and SMN2 copy number variations (CNVs) and sporadic amyotrophic lateral sclerosis (SALS) by a meta-analysis.

Methods: Through searching PubMed and EMBASE database (or manual searching) up to November 2013 using the following keywords: "survival motor neuron gene", "SMN", and "amyotrophic lateral sclerosis", "ALS" or "motor neuron disease". Nine studies were identified as eligible for this meta-analysis. The association between SMN genes and the SALS risk was investigated based on SMN1 and SMN2 CNVs. The heterogeneity across the studies was tested, as was publication bias.

Results: The analysis showed significant association for SMN1 duplications in SALS risk: the risk estimates were OR=1.76, 95%CI=1.33-2.32, p<0.0001 (still significant when the p value was Bonferroni adjusted to 0.01). However, there was no significant association between SMN1 deletions and SALS risk after Bonferroni correction (OR=1.78, 95%CI=1.02-3.11, p=0.04). In addition, SMN2 copy number statuses were not associated with SALS in our pooled study. No evidence of publication bias was observed.

Conclusion: Our meta-analysis suggested that SMN1 duplications are a genetic risk factor in SALS, while there was no modulator effect of the SMN2 gene. In addition, it was possible that SMN1 deletions in predisposition to SALS vary across different countries. More studies were required to warrant the findings of this study.

Keywords: Copy number variants; Meta-analysis; SALS; SMN1 deletions; SMN1 duplications; SMN2 homozygous deletions; Susceptibility.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • DNA Copy Number Variations
  • Databases, Factual / statistics & numerical data
  • Genetic Predisposition to Disease*
  • Humans
  • Survival of Motor Neuron 1 Protein / genetics*


  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein