1. Association Analysis of Noncoding Variants in Neuroligins 3 and 4X Genes with Autism Spectrum Disorder in an Italian Cohort
- Author
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Landini, Martina, Merelli, Ivan, Raggi, M. Elisabetta, Galluccio, Nadia, Ciceri, Francesca, Bonfanti, Arianna, Camposeo, Serena, Massagli, Angelo, Villa, Laura, Salvi, Erika, Cusi, Daniele, Molteni, Massimo, Milanesi, Luciano, Marabotti, Anna, and Mezzelani, Alessandra
- Subjects
Male ,0301 basic medicine ,Candidate gene ,Neuronal ,Autism Spectrum Disorder ,Gene Expression ,neuroligins ,lcsh:Chemistry ,0302 clinical medicine ,Gene Frequency ,Odds Ratio ,Heritability of autism ,genetics ,Child ,lcsh:QH301-705.5 ,Spectroscopy ,Genetics ,Single Nucleotide ,General Medicine ,3. Good health ,Computer Science Applications ,Italy ,Autism spectrum disorder ,Child, Preschool ,Female ,SNPs ,Cell Adhesion Molecules, Neuronal ,autism ,haplotype analysis ,noncoding regions ,Nerve Tissue Proteins ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Alleles ,Case-Control Studies ,Genetic Association Studies ,Haplotypes ,Humans ,Membrane Proteins ,Sex Factors ,Genetic Predisposition to Disease ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,mental disorders ,medicine ,Polymorphism ,Physical and Theoretical Chemistry ,1000 Genomes Project ,Preschool ,Molecular Biology ,Genetic association ,Organic Chemistry ,Haplotype ,medicine.disease ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Autism ,Cell Adhesion Molecules ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2016