Association of oligodendrocytes differentiation regulator gene DUSP15 with autism
Objectives: Autism is a pervasive neurodevelopmental disorder with high heritability. Genetic factors play crucial roles in the aetiology of autism. Dual specificity phosphatase 15 (DUSP15) has been recognised as a key regulator gene for oligodendrocytes differentiation. A previous study detected one de novo missense variant (p.Thr107Met) with probable deleterious function in exon 6 of DUSP15 among patients with autism. Therefore, we sequenced this mutation in autistic children and performed an association analysis between DUSP15 polymorphisms and autism.
Methods: We performed a case–control study between 255 children affected with autism and 427 healthy controls. Four tag-single nucleotide polymorphisms (SNPs) were selected. These SNPs and the previously reported mutation in exon 6 of DUSP15 were genotyped via Sanger sequencing.
Results: Our results showed that rs3746599 was significantly associated with autism under allelic, additive and dominant models, respectively (χ2 = 9.699, P = 0.0018; χ2 = 16.224, P = 0.001; χ2 = 7.198, P = 0.007). The association remained significant after Bonferroni correction and permutation tests (n = 10,000). We did not detect the missense variant p.Thr107Met reported in previous studies. However, a de novo missense variant of DUSP15 (p.Ala56Thr) with a probable disease-causing effect was detected in one autistic child while absent in healthy controls.
Conclusions: Our findings initially suggest that DUSP15 might be a susceptibility gene for autism in Chinese Han population.
