Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism

Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism

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 invol...

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Main Authors: Li, Jun, Zhao, Linnan, You, Yang, Lu, Tianlan, Jia, Meixiang, Yu, Hao, Ruan, Yanyan, Yue, Weihua, Liu, Jing, Lu, Lin, Zhang, Dai, Wang, Lifang
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512676/
id pubmed-4512676
recordtype oai_dc
spelling pubmed-45126762015-07-24 Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism Li, Jun Zhao, Linnan You, Yang Lu, Tianlan Jia, Meixiang Yu, Hao Ruan, Yanyan Yue, Weihua Liu, Jing Lu, Lin Zhang, Dai Wang, Lifang Research Article 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. Public Library of Science 2015-07-23 /pmc/articles/PMC4512676/ /pubmed/26204268 http://dx.doi.org/10.1371/journal.pone.0133247 Text en © 2015 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Li, Jun
Zhao, Linnan
You, Yang
Lu, Tianlan
Jia, Meixiang
Yu, Hao
Ruan, Yanyan
Yue, Weihua
Liu, Jing
Lu, Lin
Zhang, Dai
Wang, Lifang
spellingShingle Li, Jun
Zhao, Linnan
You, Yang
Lu, Tianlan
Jia, Meixiang
Yu, Hao
Ruan, Yanyan
Yue, Weihua
Liu, Jing
Lu, Lin
Zhang, Dai
Wang, Lifang
Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
author_facet Li, Jun
Zhao, Linnan
You, Yang
Lu, Tianlan
Jia, Meixiang
Yu, Hao
Ruan, Yanyan
Yue, Weihua
Liu, Jing
Lu, Lin
Zhang, Dai
Wang, Lifang
author_sort Li, Jun
title Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
title_short Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
title_full Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
title_fullStr Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
title_full_unstemmed Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism
title_sort schizophrenia related variants in cacna1c also confer risk of autism
description 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.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512676/
_version_ 1613251370493673472

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