Research On The Association Between Brain-Derived Neurotrophic Factor Gene And Young Major Depressive Disorder

Objecive:Major depressive disorder(MDD)is a common mental illness that brings a heavy burden to society and families.Adolescence is considered the peak age for the emergence of MDD,and the onset of youth depression may be related to neurodevelopment.Brain-Derived Neurotrophic Factor(BDNF)plays an important role in the development,maturation and maintenance of the physiological function of the nervous system.Studies have found that BDNF may participate in the occurrence of MDD by mediating neurodevelopment.Both rare and common variants in genes can increase the genetic risk of MDD.A large number of studies have focused on the relationship between MDD and common variants of BDNF gene.However,the relationship between young MDD patients and rare mutations of BDNF gene is unclear.The objective of this study is to explore the association between common and rare variants of BDNF gene and MDD patients.Methods:(1)A total of 105 MDD patients and 154 healthy controls aged 13-25 years old were collected.All of the MDD patients met the diagnostic criteria of DSM-IV.The Fast Target method was used to sequence the BDNF genes of all subjects.The sequencing region of BDNF gene includes: exon region,promoter region,exon-intron boundary region,5’UTR and 3’UTR.(2)Fast QC software was used to evaluate the quality of the original sequencing data.BWA v0.7.15-r1140 software was used to compare the original sequencing data.Picard software was used to make statistics on the comparison results of the samples.The GATK standard software was used to correct the preliminary comparison results of the BWA software.Var Scan v2.3.9 software and GATK Haplotype Caller software were used to detect single nucleotide variations/insertions in each sample.Use ANNOVAR to analyze all mutation sites.(3)SPSS 26.0 was used to perform independent-sample t-test and χ2 test for age and gender between the two groups.PLINK 1.07 software was used to analyze the genotype frequency and allele frequency of the SNP between the two groups,the χ2 test was used to perform the Hardy-Weinberg genetic balance test,and compare the genotype and allele frequency between the two groups,Logestic regression was used to adjusted for age.The Haploview software was used to analyze the linkage disequilibrium of SNPs,and the haplotype frequency between the two groups was compared by the χ2 test.Generalized multi-factor dimensionality reduction software was used to analyze the SNP-SNP interaction.FDR was used to correct the P value.P<0.05 is statistically significant.Results:(1)Common variants: A total of 10 common functional variants were found in the target region of the BDNF gene.Among them,the variant rs4030470 was associated with the MDD of the Chinese Han young people(P = 0.046).But this was no longer significant after applying a FDR correction(P= 0.552,after FDR correction),and the remaining 9 SNPs are not related to young MDD.Haplotype analysis found that the three haplotypes of the BDNF gene were not associated with young MDD.SNP-SNP interaction analysis showed that there was no interaction between the 10 SNPs of the BDNF gene in young MDD patients;(2)Short tandem repeat: We found a short tandem repeat rs3838785,but there is no relationship between this variant and young MDD.(3)Rare variants: No rare variant of BDNF gene was found in all the subjects in this study.Conclusion: In this study,we did not find an association between common or rare variants of BDNF gene and young Chinese Han MDD patients.