Identification of CDH11 as an ASD risk gene by matched-gene co-expression analysis and mouse behavioral studies
AbstractIn the study of autism spectrum disorder (ASD) by gene co-expression analysis (GCA), we found that four gene features, including gene size, mRNA length, mRNA abundance, and guanine-cytosine content, profoundly affect gene co-expression profiles. To circumvent the potential interference of these confounding factors on GCA, we developed the “matched-gene co-expression analysis” (MGCA) to investigate gene co-expression relationships. This method demonstrated the convergent expression profile of high confidence ASD risk genes and effectively revealed convergent molecular pathways of ASD risk genes. Application of MGCA to two ASD candidate genes CDH11 and CDH9 showed association of CDH11, but not CDH9, with ASD. Mouse behavioral studies showed that Cdh11-null mice, but not Cdh9-null mice, have multiple autistic-like behavioral alterations. This study confirmed that CDH11 is an important ASD risk gene and demonstrated the importance of considering matched gene features in the analysis of gene co-expression.