The Study Of BRWD3 And GATA4 Affecting Human Cognitive Ability

Cognitive ability is acritical psychological potential for human activity.Previous studies demonstrated that cognitive ability is heritable and regulated by many genes. While the mechanism through which cognitive ability is regulated remains elusive.BRWD3 gene involves in chromatin modification,and may play a role in regulation of transcription. Loss of function of BRWD3 resulted in mental retardation.However,whether BRWD3 involved in regulation of human cognitive ability in nomal development and what is the mechanism is unclear.In this study, we investigated the relationship between polymorphism rs12557771 of BRWD3and human cognitive ability with the behavioral genomics method.Then, gene clone and dual luciferase reporter system was used to assess the transcription activity of the different rs12557771 polymorphism.We predicted that BRWD3 expression is regulated by GATA4 by using bioinformatics analysis. We further explored the relationship of GATA4 gene polymorphism with human cognitive ability and the combination analysis of GATA4 and BRWD3 gene withhuman cognitive ability.Our results showed that:(1) rs12557771 in the promoter region of BRWD3 gene was significantly associated with reasoning mean reaction time (p=0.037),and it had a positive correlation with semantic fluency (p=0.051) and error rates of sentence-picture matching (p=0.058) in males. These three tests are all belonged to verbal cognitive ability and the p values are all corrected.(2)The single locus association analysis between GATA4 gene and human cognitive ability showed that the polymorphism of rs6601604 had a significantly effect on visuo-spatial working memory span (p=0.021) in females; rs17153755 polymorphism only had a positive correlation with Raven test of general fluid intelligence (p=0.081) and females’ semantic fluency of verbal cognitive ability (p=0.087); rs12825 polymorphism had a significant influence on error rates of sentence-picture matching belonged to verbal cognitive ability (p=0.015) in females, it also had a positive correlation with visuo-spatial working memory mean reaction time (p=0.081).All the p values were corrected.(3)Combination analysis of GATA4gene and BRWD3 gene on the effect of verbal cognitive ability indicated thatrsl2825*rs12557771 had a positive correlation with semantic fiuencyin males.(4)Summary of the mechanism study of BRWD3 gene in regulation of human cognitive ability:Luciferase activity of each expression vector measured by dual luciferase reportor system was pairwise-comparised. Results from statistic analysis showed that there was a significant difference between the Empty-Prom and A allele or G allele of rs12557771 expression vector(p<0.05), while the luciferase activity between A allele and G allele of rs12557771 expression vector showed no significant difference (p=0.1561).Our results indicate that BRWD3 is associated with human verbal cognitive ability; GATA4plays an important role in human verbal cognitive ability and working memory; interaction between GATA4and BRWD3 has a positive correlation with human verbal cognitive ability; polymorphism of rsl2557771 in BRWD3 promoter region is not enough to impact BRWD3 expression; the mechanism through which human cognitive ability regulated by BRWD3 needed further study.