title: Common Regulatory Variants of CYFIP1 Contribute to Susceptibility for Autism Spectrum Disorder (ASD) and Classical Autism.
abstract: Based on the analysis of mRNA expression and genotype data from the "Brain Cloud" database, we identified seven SNPs within or near the autism candidate gene CYFIP1 that show nominally significant correlations between genotype and CYFIP1 mRNA expression in human dorsolateral prefrontal cortex. Analysis of transmission disequilibrium test (TDT) odds ratios (ORs) for these SNPs in a large Autism Genome Project (AGP) trio-based association study revealed the high-expression alleles of four of these SNPs (rs8028440, rs2289823, rs7403800 and rs3751566) to be susceptibility alleles. Correlations between the regression coefficients for mRNA expression and log10-transformed TDT ORs were statistically significant [P = 0.008 (ASD); P = 0.002 (classical autism)]. Similarly, statistically significant correlations were obtained between levels of CYFIP1 mRNA expression predicted using the regression equations obtained from multiple linear regression analysis and log10-transformed TDT ORs for specific combinations of genotypes for both ASD (rs2289823 + rs3751566: P = 0.008) and classical autism (rs2289823 + rs3751566: P = 0.008; rs2289823 + rs3751566 + rs765763: P = 0.0006) diagnoses. Together, these results support the hypothesis that high expression of CYFIP1 mRNA increases susceptibility for both ASD and classical autism.
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.|Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Shanghai, Ministry of Education, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cellular and Genetic Medicine, Fudan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Cellular and Genetic Medicine, Fudan University, Shanghai, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Song
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Psychology, Chinese Academy of Science, Beijing, China.
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.affiliation: Institutes of Brain Science, Fudan University, Shanghai, China.|School of Life Sciences, Fudan University, Shanghai, China.|Department of Cellular and Genetic Medicine, Fudan University, Shanghai, China.|State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: David
authors.initials: D
authors.lastname: Saffen
keywords: CYFIP1; autism spectrum disorder; expression quantitative locus (eQTL); regulatory genetic variant