Dataset Information

Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.

ABSTRACT: Schizophrenia is a severe mental disorder affecting ?1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia.

SUBMITTER: Shi Y

PROVIDER: S-EPMC3773910 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.

Shi Yongyong Y Li Zhiqiang Z Xu Qi Q Wang Ti T Li Tao T Shen Jiawei J Zhang Fengyu F Chen Jianhua J Zhou Guoquan G Ji Weidong W Li Baojie B Xu Yifeng Y Liu Dengtang D Wang Peng P Yang Ping P Liu Benxiu B Sun Wensheng W Wan Chunling C Qin Shengying S He Guang G Steinberg Stacy S Cichon Sven S Werge Thomas T Sigurdsson Engilbert E Tosato Sarah S Palotie Aarno A Nöthen Markus M MM Rietschel Marcella M Ophoff Roel A RA Collier David A DA Rujescu Dan D Clair David St DS Stefansson Hreinn H Stefansson Kari K Ji Jue J Wang Qingzhong Q Li Wenjin W Zheng Linqing L Zhang Hairong H Feng Guoyin G He Lin L

Nature genetics 20111030 12

Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the ...[more]

PMID: 22037555

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Project 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.

Dataset Information

Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.

Publications

Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.

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