ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Carpentier, P. J., 201222841130
Citation	Carpentier, P. J., A. Arias Vasquez, M. Hoogman, M. Onnink, C. C. Kan, J. J. Kooij, R. Makkinje, S. Iskandar, L. A. Kiemeney, C. A. de Jong, B. Franke and J. K. Buitelaar (2012). "Shared and unique genetic contributions to attention deficit/hyperactivity disorder and substance use disorders: A pilot study of six candidate genes." Eur Neuropsychopharmacol.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	176 patients and 500 controls
Predominant Ethnicity	Caucasian
Population	Dutch
Gender	47.7% men with ADHD, 49.4% men controls
Age Group	Adults : mean age 37.1 years, age range18-65 of Adult ADHD patients; mean age 59.4 years, age range 22-92 of controls

Detail Info

Summary	The shared genetic basis of attention deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) was explored by investigating the association of candidate risk factors in neurotransmitter genes with both disorders. One hundred seven methadone maintenance treatment patients, 36 having an ADHD diagnosis, 176 adult patients with ADHD without SUDs, and 500 healthy controls were genotyped for variants in the DRD4 (exon 3 VNTR), DRD5 (upstream VNTR), HTR1B (rs6296), DBH (rs2519152), COMT (rs4680; Val158Met), and OPRM1 (rs1799971; 118A>G) genes. Association with disease was tested using logistic regression models. This pilot study was adequately powered to detect larger genetic effects (OR>/=2) of risk alleles with a low frequency. Compared to controls, ADHD patients (with and without SUDs) showed significantly increased frequency of the DBH (rs2519152: OR 1.73; CI 1.15-2.59; P=0.008) and the OPRM1 risk genotypes (rs1799971: OR 1.71; CI 1.17-2.50; P=0.006). The DBH risk genotype was associated with ADHD diagnosis, with the association strongest in the pure ADHD group. The OPRM1 risk genotype increased the risk for the combined ADHD and SUD phenotype.
Total Sample	All the patients were ethnic Caucasian.Screening for SUDs was part of the clinical evaluation.
Sample Collection	Adult patients with persistent ADHD were recruited as part of the International Multicentre Persistent ADHD CollaboraTion(IMpACT) from two treatment centres in The Netherlands. Controls of Caucasian origin were recruited as part of the Nijmegen Biomedical Study, a population-based survey conducted by the Department of Epidemiology and Biostatistics and the Department of Clinical Chemistry of the Radboud University Nijmegen Medical Centre.
Diagnosis Description	All patients were evaluated by experienced psychiatrists; the diagnosis of persistent ADHD was based on DSM-IV criteria.
Technique	Genotyping was performed on DNA isolated from blood or saliva using standard protocols. Genotyping of DRD4 (exon 3VNTR)and DRD5 (upstream VNTR) was performed using Fragment Length Analysis. The HTR1B polymorphism rs6296 was genotyped using a Taqman analysis. The DBH polymorphism rs2519152 was genotyped using a restriction-fragment length polymorphism(RFLP) analysis. The COMT polymorphism(rs4680) was genotyped using Taqman analysis. The OPRM1 polymorphism (rs1799971)was genotyped again using Taqman analysis.
Analysis Method	Hardy-Weinberg equilibrium(HWE) was assessed for each genetic variant tested using standard methods and using a p-valu e cut-off of 0.05. To analyse the association between the selected genetic variants and the risk of ADHD,a logistic regression was performed comparing the ADHD_all group and the control group with gender as the covariate.To account for multiple analyses,the significance level was adjusted using a Bonferroni correction All statistical analyses were performed using Statistical Package for the Social Sciences 15.0.1, 2006 (SPSSInc.,Chicago,Ill.,USA).
Result Description	This pilot study was adequately powered to detect larger genetic effects (OR>/=2) of risk alleles with a low frequency. Compared to controls, ADHD patients (with and without SUDs) showed significantly increased frequency of the DBH (rs2519152: OR 1.73; CI 1.15-2.59; P=0.008) and the OPRM1 risk genotypes (rs1799971: OR 1.71; CI 1.17-2.50; P=0.006). The DBH risk genotype was associated with ADHD diagnosis, with the association strongest in the pure ADHD group. The OPRM1 risk genotype increased the risk for the combined ADHD and SUD phenotype. The present study strengthens the evidence for a shared genetic basis for ADHD and addiction. The association of OPRM1 with the ADHD and SUD combination could help to explain the contradictory results of previous studies. The power limitations of the study restrict the significance of these findings: replication in larger samples is warranted.

SNPs reported by this study (count: 4)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs1799971	A>G	G	genotypic P-value=0.006, adj OR=1.71, 95%CI=1.17-2.50; P-value=0.50, adj OR=1.12, 95%CI=0.81-1.54 with gender as the covariate	After the Bonferroni correction, a significant association w...... After the Bonferroni correction, a significant association with disease was found for the DBH (OR 1.73;CI1.15-2.59; P=0.008)and the OPRM1 (OR 1.71;CI1.17-2.50; P=0.006) risk genotypes. The covariate Gender had no significant effect. More...	Significant
rs2519152	C>T	C	genotypic P-value=0.008, adj OR=1.73, 95%CI=1.15-2.59; P-value=0.48, adj OR=1.13, 95%CI=0.80-1.60 with gender as the covariate	After the Bonferroni correction, a significant association w...... After the Bonferroni correction, a significant association with disease was found for the DBH (OR 1.73;CI1.15-2.59; P=0.008)and the OPRM1 (OR 1.71;CI1.17-2.50; P=0.006) risk genotypes. The covariate Gender had no significant effect. More...	Significant
rs4680	G>A	G	genotypic P-value=0.93, adj OR=1.02, 95%CI=0.70-1.48; P-value=0.42, adj OR=1.15, 95%CI=0.82-1.62 with gender as the covariate	No significant association was found for the risk allele car...... No significant association was found for the risk allele carriers in the ADHD_all group compared to the control group. The covariate Gender had no significant effect. More...	Non-significant
rs6296	G>C	C	genotypic P-value=0.69, adj OR=0.94, 95%CI=0.68-1.29; P-value=0.54, adj OR=1.10, 95%CI=0.80-1.53 with gender as the covariate	No significant association was found for the risk allele car...... No significant association was found for the risk allele carriers in the ADHD_all group compared to the control group. The covariate Gender had no significant effect. More...	Non-significant

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DRD4 exon3 VNTR		7R	genotypic P-value=0.16, adj OR=0.78, 95%CI=0.55-1.10; P-valu...... genotypic P-value=0.16, adj OR=0.78, 95%CI=0.55-1.10; P-value=0.58, adj OR=1.10, 95%CI=0.79-1.52 with gender as the covariate More...	No significant association was found for the risk allele carriers in the ADHD_all group compared to the control group. The covariate Gender had no significant effect.	Non-significant
DRD5 upstream (TC)n		148bp	genotypic P-value=0.066, adj OR=0.70, 95%CI=0.18-1.02; P-val...... genotypic P-value=0.066, adj OR=0.70, 95%CI=0.18-1.02; P-value=0.38, adj OR=1.17, 95%CI=0.82-1.66 with gender as the covariate More...	No significant association was found for the risk allele carriers in the ADHD_all group compared to the control group. The covariate Gender had no significant effect.	Non-significant

Genes reported by this study (count: 6)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DRD4	No significant association was found. No significant association was found.	Non-significant
HTR1B	No significant association was found. No significant association was found.	Non-significant
DBH	The DBH risk genotype was associated with ADHD diagnosis, wi...... The DBH risk genotype was associated with ADHD diagnosis, with the association strongest in the pure ADHD group. More...	Significant
DRD5	No significant association was found. No significant association was found.	Non-significant
COMT	No significant association was found. No significant association was found.	Non-significant
OPRM1	The OPRM1 risk genotype increased the risk for the combined ...... The OPRM1 risk genotype increased the risk for the combined ADHD and SUD phenotype. More...	Significant