An Association Study Of Psychological Behavior Problems With Dopamine Receptor Gene Single Nucleotide Polymorphism And Environmental Factors In 4-12-year-old Twins

As a common phenomenon in the development of children,child psychological behavior problems can predict the psychological behavior problems in adolescence and even adulthood to a certain extent.The aims of the study were to understand the genetic and environmental effects of psychological behavior problems of preschool and school-age twins,the impact of single nucleotide polymorphism and haplotype of dopamine receptor gene,and the interaction between gene and environment on psychological behavior problems.The psychological behavior problems were measured with Achenbach Child Behavior Checklist(CBCL)in 261pairs twins aged 4-12 years old in Hohhot and Baotou,Inner Mongolia.Genomic DNA was isolated from cotton-tipped swabs using a genomic DNA extraction and purification kit.16 single nucleotide polymorphisms(SNPs)selected from dopamine receptors were genotyped using SNaPshot.The heritability of psychological behavior problems were calculated by Holzinger and Mx software.SPSS Statistics 18.0(SPSS Inc.,Chicago,IL,USA)of?~2,ANOVA,independent sample t-test,binary logistic regression,multiple linear regression,and generalized estimating equations were employed to analyze the factors affecting psychological behavior problems.Linkage disequilibrium and haplotype analysis for 16 SNPs were assessed using Haploview 4.2 and Phase software,respectively.Generalized estimating equations was used to analyze the association haplotypes and psychological behavior problems.The results showed that:(1)The total incidence rate of“psychological behavior problems”in 4-12-year-old twins was 23.60%(male 24.80%,female 22.30%).(2)Among 4-12-year-old twins,the heritability(75.00%)of the occurrence of“anxious/depressed”was high,and the heritability of“attention problem scores”(male 69.00%,female 73.00%)and“aggressive behavior scores”(male 62.00%,female 68.00%)were also higher than those of other psychological behavior problems.In addition,the heritability of“attention problem scores”(male 85.00%,female 92.00%)and“social problems scores”(female 72.00%)were high at the age of 4-6 years old,“withdrawal behavior”(female 83.00%),“attention problem”(male81.00%,female 92.00%),and“aggressive behavior”(male 66.00%,female66.00%)at the age of 6-9 years old,and“anxious/depressed”(female70.00%),“withdrawal behavior”(male 61.00%,female 60.00%),“somatic complaints”(female 65.00%),“thought problems”(male 91.00%,female79.00%),and“aggressive behavior”(male 78.00%,female 73.00%)at the age of 10-12 years old respectively.(3)The main factors influencing the psychological behavior problems of children were the characteristics of children such as gender,age,and temperament,demographic characteristics such as parents'occupation,education level,and childbearing age,and family environment and function characteristics such as family adaptability,cohesion,and parenting styles(p(27)0.05).Moreover,family cohesion interaction with children's temperament and father's education level on“total behavior problems”respectively.And the parenting styles interaction with“somatic complaints”and“aggressive behavior”(p(27)0.05).(4)In psychological behavior problems occur or not,rs7131056 was associated with“anxious/depressed”(p(27)0.05);rs6279,rs4274224,rs1967551,rs1079727,and rs267418 were associated with“thought problems”(p(27)0.05);rs6279 was associated with“delinquent behavior”and“somatic complaints”(p(27)0.05).In the scores of psychological behavior problems,rs752306,rs1967551,rs265973,and rs1079595 were associated with“somatic complaints”;rs1967551 and rs1079595 were associated with“attention problems”;rs1079727 and rs267418 were associated with“aggressive behaviors”(p(27)0.05);rs1079727 was associated with“externalization behaviors”;rs6279,rs1079727,rs936461,and rs267418 were associated with“total behavior problems”(p(27)0.05).In addition,the impact of interaction between rs4274224 and gender on“thought problems”(p(27)0.05);the interaction between rs6279 with rs1079727 and rs267418 on“introversion behaviors”respectively(p(27)0.05).(5)The haplotype G-A-G composed of rs6279-rs1079595-rs1079727 was associated with“anxious/depressed”,and“attention problems”(p<0.05);C-C-A was related to“disciplinary behaviors”(p<0.05).The main conclusions of this study are as follows:(1)Children's“anxious/depressed”,“attention problems”,and“aggressive behavior”were mainly affected by heredity,other behavior factors were mainly affected by environmental effects,and it was showed on developmental stage characteristics in the relative effects of genetics and environment.(2)Children's psychological behavior problems were mainly affected by environmental factors such as children's own characteristics,parents'demographic characteristics,family environment and function,and genetic factors(mainly single nucleotide polymorphism and haplotype of DRD2 gene).And the interaction between environmental and genetic in psychological behavior problems conforms to the"difference sensitivity"model.