Gastrointestinal Phenotypes In ASD And Phenotype-Genotype Association Study

Objective: To explore the detection rate of gastrointestinal(GI)problems in Chinese Autism Spectrum Disorder(ASD)children,and the association between GI problems and ASD relative symptoms.Futher more,to explore the SNP sites and candidate genes associated with GI phenotype in ASD children,in order to preliminarily undertand the genetic risk factor of this problem.Method:336 ASD children aged from 3-8 years old were recruited to the study according to the inclusion and exclusion criteria.General information about the children,including birth date,gender,food allergy history,gastrointestinal problems during recent 3 months and socialpsychological scales,were comleted by parents or caretakers.The detection rate of GI problems was calculated in this population,and the association between GI problems and ASD relative symptoms was analyzed.Further more,genetic evaluation was taken by 254 individuals in this sample(69 ASD with GI problems and 185 ASD without GI problems)using Affymetrix Cytoscan HD chips.To screen out SNP sites and its involving protein-coding genes though SNP analysis.Then according to gene expression pattern and function annotation,we screened out candidate genes of GI phenotype in ASD.Finally we analyzed the association between the candidate genes and neurodevelopmental as well as gastrointestinal disorders,and underlying molecular pathways.Result : 1.Among 336 ASD individuals,gastrointestinal problems were detected in 85 children.General GI problem detection rate is 25.3%?Specifically,59 children with constipation(17.6%),12 children with vomiting(3.6%),11 children with diarrhea(3.3%),7children with abdominal pain(2.1%),and 6 children with abdominal bloating(1.8%).There was no difference between different age distribution.GI problem was significantly associated with sensory over-reponsitivity(t=3.172,p<0.05),as well as emotional problems(t=-3.215,p<0.05).2.Using Affymetrix Cytoscan HD chips,we screened out 18 SNP sites associated with GI phenotype in ASD,involving 15 protein-coding genes.Then according to gene expression pattern and function annotation,we screen out 2 candidate genes of GI phenotype in ASD--CDH2,MAGED1.Accompanying with co-expression genes,the candidate genes contributed to thephenotype through ‘gut-brain axis' relative molecular pathways,such as Degradation of beta-catenin by the destruction complex,etc.Conclusion:GI problems were often seen in Chinese ASD children,with the highest detection rate of constipation.And GI problems persistently occurred during 3-8 years old in this group of children,indicating more concern about GI problems in ASD children.GI problems was significantly associated with sensory overreponsitivity,as well as emotional problems,implying that resolving GI problems may be helpful to remit these problems.By phenotype-genotype association analysis,we screened out CDH2 and MAGED1 as candidate genes of GI phenotype in ASD children.We speculated that,accompanying with co-expression genes,the candidate genes contributed to the phenotype through ‘gut-brain axis' relative molecular pathways.