Work

Common Regulatory Variants ofCYFIP1Contribute to Susceptibility for Autism Spectrum Disorder (ASD) and Classical Autism

Year: 2015

Type: article

Abstract: Summary 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 geneCYFIP1that show nominally significant correlations between genotype andCYFIP1mRNA 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 ofCYFIP1mRNA 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 ofCYFIP1mRNA increases susceptibility for both ASD and classical autism.

Source: Annals of Human Genetics

DOI: 10.1111/ahg.12121

Authors: Jian Wang, Yu Tao, Fan Song, Yue Sun, Jurg Ott, David Saffen