Association analysis of noncoding variants in neuroligins 3 and 4X genes with autism spectrum disorder in an Italian cohort

Martina Landini, Ivan Merelli, M. Elisabetta Raggi, Nadia Galluccio, Francesca Ciceri, Arianna Bonfanti, Serena Camposeo, Angelo Massagli, Laura Villa, Erika Salvi, Daniele Cusi, Massimo Molteni, Luciano Milanesi, Anna Marabotti, Alessandra Mezzelani

Research output: Contribution to journalArticlepeer-review


Since involved in synaptic transmission and located on X-chromosome, neuroligins 3 and 4X have been studied as good positional and functional candidate genes for autism spectrum disorder pathogenesis, although contradictory results have been reported. Here, we performed a case-control study to assess the association between noncoding genetic variants in NLGN3 and NLGN4X genes and autism, in an Italian cohort of 202 autistic children analyzed by high-resolution melting. The results were first compared with data from 379 European healthy controls (1000 Genomes Project) and then with those from 1061 Italian controls genotyped by Illumina single nucleotide polymorphism (SNP) array 1M-duo. Statistical evaluations were performed using Plink v1.07, with the Omnibus multiple loci approach. According to both the European and the Italian control groups, a 6-marker haplotype on NLGN4X (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, p-value = 2.58 × 10−6 for the European controls; odds ratio = 2.42, p-value = 6.33 × 10−3 for the Italian controls). Furthermore, several haplotype blocks at 5-, 4-, 3-, and 2-, including the first 5, 4, 3, and 2 SNPs, respectively, showed a similar association with autism. We provide evidence that noncoding polymorphisms on NLGN4X may be associated to autism, suggesting the key role of NLGN4X in autism pathophysiology and in its male prevalence.

Original languageEnglish
Article number1765
JournalInternational Journal of Molecular Sciences
Issue number10
Publication statusPublished - Oct 1 2016


  • Autism
  • Genetics
  • Haplotype analysis
  • Neuroligins
  • Noncoding regions
  • SNPs

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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