The Candidate Gene Study Of Post Stroke Depression In Chinese Han Population By Targeted Sequencing

Background and objective: Both stroke and depression are multi-factorial diseases,with both genetic and environmental factors likely to participate in their pathogenesis.Post stroke depression(PSD)is a common complication after stroke leading to poor functional outcome,increased physical disability and mortality.Although several genes have been associated with PSD,the genetic basis and associated pathophysiological processes of PSD remain poorly understood.This study was aimed to find novel candidate genes for PSD in Chinese Han population through targeted sequencing of genes in multiple pathways.Method: A 2-stage candidate gene study by targeted sequencing was conducted involving stroke patients with or without depression and health controls.In the discovery stage(121 PSD,131 non-PSD and 639 HC),logistic regression was used to test associations respectively in PSD and non-PSD groups.In the replication stage(200 PSD,218 non-PSD and 983 HC),54 selected SNPs were again genotyped in an independent cohort.Fixed-effects inverse variance-weighted meta-analysis was used in the combined samples.In addition,annotation,functional network analysis and enrichment analysis were conducted.Results: The study identified 2 novel susceptibility genes associated with PSD [HTR3D(rs55674402,p=0.002512,odds ratio(OR)=0.7431);NEUROG3(rs144643855,p=0.00325,OR=0.6523)] and 3 risk SNPs in one gene significantly associated with non-PSD(PIK3C2B,rs17406271,p=0.0006801,OR=1.446;rs2271419,p=0.0005836,OR=1.497;rs2271420,p=0.001031,OR=1.431).NEUROG3 shows highest expression level in hippocampus.Functional enrichment analysis showed that susceptibility genes of PSD are mostly enriched in chemical synaptic transmission and regulation of lipid synthetic process.Conclusion: This study identified that HTR3 D and NEUROG3 were linked with the susceptibility of PSD and PIK3C2 B with stroke in the Chinese stroke population.Functional analysis suggested that the pathogenesis of PSD might be implicated in 5-HT synaptic transmission,neural plasticity and lipid metabolism and therapeutic interventions targeting these pathways may be effective approaches for PSD treatment.Considering several limitations in sample size and matching,further replication of these findings in a larger and better matched sample is warranted.