Genetic Exploration Of Bipolar Disorder In Chinese Population Using Whole Exome Sequencing

Bipolar disorder(BD)is a kind of mental disease that is susceptible to both genetic and environmental factors.BD affects over one percent of population around the world.BD not only decreases life quality,but also lead to huge social and economic burden.The exact mechanisms underlying BDs largely remain uncertain yet due to the medical complexity.Prior genetic studies estimated the heritability of BDs up to about 80%.A number of GWAS found several susceptible variants,which can explain about 10%to 20%BDs.Besides,the application of exome sequencing help finding rare mutations in BD.However,most of these efforts focus on either Caucasian or isolated population.The genetic characteristics in Chinese bipolar disorder patients still remain unexplored.In this study,we cooperated with the local mental hospital for genetic understanding of BDs.We carefully selected 22 BD patients who were diagnosed as"Bipolar disorder,current episode manic without psychotic features".The patients also showed positive responses to the treatment of olanzapine and valproate.We selected twelve patients samples for whole exome sequencing(WES).Using 1000 Genome and ExAC allele frequency spectrum as reference,we identified a list of potential genetic variations associated with BD.Furthermore,we validated and refined the genetic variations associated with BD by another ten patients' WES data.Eventually,we archieved 113 single nucleotide variations(SNVs)and 20 indels that show strong associated with BD.These genetic variations cover 94 genes like GPRIN2,RHBG,MUC12 and so on.Additional analysis showed that these genes do have some connections with BD in either function or its chromosome locus.For example,BD were proved susceptible to 1p36,1q22,Xq27-q28,GPRIN2 and MUC12 in previous study.In summary,we identified several genetic variations associated with BDs in Chinese population.These findings may be helpful in prompting our molecular understanding of BD;it will also aid better diagnosis and treatment of BDs.