Ye Tian1,2,3, Lifang Wang1,2,3, Meixiang Jia1,2,3, Tianlan Lu1,2,3, Yanyan Ruan1,2,3, Zhiliu Wu1,2,3, Linyan Wang1,2,3, Jing Liu1,2,3, Dai Zhang1,2,3,4. 1. a Institute of Mental Health, Peking University , Beijing , PR China. 2. b Peking University Sixth Hospital , Beijing , PR China. 3. c Key Laboratory for Mental Health , Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University) , Beijing , PR China. 4. d PKU-IDG/McGovern Institute for Brain Research, Peking University , Beijing , PR China.
Abstract
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.
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 autisticchildren 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 autisticchild while absent in healthy controls. CONCLUSIONS: Our findings initially suggest that DUSP15 might be a susceptibility gene for autism in Chinese Han population.