title: Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.
abstract: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic component. Many lines of evidence indicated that ASD shares common genetic variants with other psychiatric disorders (for example, schizophrenia). Previous studies detected that calcium channels are involved in the etiology of many psychiatric disorders including schizophrenia and autism. Significant association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit) and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is suggested to cause Timothy syndrome, a multisystem disorder including autism-associated phenotype. However, there is no evidence for association between CACNA1C and autism in Chinese Han population. To investigate the association between single nucleotide polymorphisms (SNP) in CACNA1C and autism, we first performed a family-based association study between eighteen SNPs in CACNA1C and autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping platform. Two SNPs (rs1006737 and rs4765905) have a trend of association with autism. To further confirm the association between these two SNPs with autism, we expanded the sample size to 553 trios by adding 314 trios. Association analyses for SNPs and haplotype were performed by using family-based association test (FBAT) and Haploview software. Permutation tests were used for multiple testing corrections of the haplotype analyses (n=10,000). The significance level for all statistical tests was two-tailed (p<0.05). The results demonstrated that G allele of rs1006737 and G allele of rs4765905 showed a preferential transmission to affected offspring in 553 trios (p=0.035). Haplotype analyses showed that two haplotypes constructed from rs1006737 and rs4765905 were significantly associated with autism (p=0.030, 0.023, respectively; Global p=0.046). These results were still significant after permutation correction (n=10,000, p=0.027). Our research suggests that CACNA1C might play a role in the genetic etiology of autism in Chinese Han population.
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Linnan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: You
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Tianlan
authors.initials: T
authors.lastname: Lu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Jia
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, P. R. China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, P. R. China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China; Key Laboratory of Mental Health, Ministry of Health & National Clinical Research Center for Mental Disorders (Peking University), Beijing, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000483:Alleles; D044466:Asian People / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000235:genetics*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type