Autism Incidence and Association with MECP2 Variants on a Positively-Selected Haplotype in North-Eastern China

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
11:00 AM
X. Zhou1,2, Y. Xu1,2,3, L. J. Wu1,2, Q. Ayub1, C. Tyler-Smith1 and Y. Xue1, (1)The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs., United Kingdom, (2)Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin, China, (3)Center for Behavioural Science, School of Medicine, Nankai University, Tianjin, China
Background:  Autism is a developmental disorder characterized by social interaction deficit, language impairment and repetitive behaviours with restricted interests. Its worldwide prevalence varies between 4.2‰ and 12.1‰, with a male: female ratio of 4:1. There is a substantial genetic contribution to autism susceptibility. However, few studies have been carried out in Chinese populations, which account for one-fifth of the world population, and it is unclear to what extent the incidence and genetic susceptibility landscape are similar to those in Western populations.

Objectives:  The objectives were to study the general epidemiological features of the autism in North-eastern of China, to replicate the association of rs2734647 in the MECP2 gene in a Chinese autism cohort collections light of the evolutionary history of this locus.

Methods: A cross-sectional investigation and stratified cluster sampling methods were used in the epidemiological study. ASD cases(n=649) and  controls (n=592) from North-eastern China were recruited in the study. A case-control association analysis was used to test the association between MECP2 rs2734647 and the Chinese Han population. Summary statistics and a likelihood ratio test were used to test the pattern of variation in resequencing data from a ~20kb region of the MECP2 gene for consistency with neutral evolution in 4 HapMap populations (YRI, LWK, CEU and CHB).

Results: Our epidemiological investigation from North-eastern China showed that the prevalence of autism was 2.27‰, rather lower than other reports. However, the male: female ratio was much higher (7.0:1). We successfully replicated the association of rs2734647 with autism (p=0.039) in our case-control collection from North-eastern China. The protective allele is present at high frequency (>80%) in the HapMap CHB and JPT samples and an evolutionary investigation showed significant departures from a neutral pattern of evolution with the Fay and Wu’s H statistic or a likelihood ratio test, indicating that it lies on a haplotype that has been positively selected in East Asian populations.  

Conclusions: MECP2 rs2734647 is also associated with autism in Chinese population and the haplotype carrying the derived allele for this variant appears to have been positively selected in early human history, but now contributes to the incidence of autism in China. The SNP which is located in a highly conserved region in the 5’ UTR of the gene, could have functional importance. 

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