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	Ribases, M., 201222404661
Citation	Ribases M., Ramos-Quiroga J. A., Hervas A., Sanchez-Mora C., Bosch R., Bielsa A., Gastaminza X., Lesch K. P., Reif A., Renner T. J., Romanos M., Warnke A., Walitza S., Freitag C., Meyer J., Palmason H., Casas M., Bayes M. and Cormand B. (2012) "Candidate system analysis in ADHD: evaluation of nine genes involved in dopaminergic neurotransmission identifies association with DRD1." World J Biol Psychiatry, 13(4): 281-92.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	Discovery cohort: Childhood ADHD sample: 322 children with ADHD and 322 sex-matched unrelated controls. 196 affected children and their parents were used for the subsequent family-based study. Discovery cohort: Adulthood ADHD sample: 211 ADHD subjects and 211 sex-matched unrelated controls. Replication cohort: 353 nuclear ADHD families from Germany
Predominant Ethnicity	Caucasian
Population	German an Spanish
Gender	Discovery cohort: Childhood ADHD sample: Seventy-nine percent of patients and controls were male. Discovery cohort: Adulthood ADHD sample: Seventy-three percent of subjects were male. Replication cohort: Eighty-two percent of probands were males.
Age Group	Children/Adolescents and Adults : Discovery cohort: Childhood ADHD sample: The average age at assessment was 9.3 years (SD=2.6) for patients and 36.8 years (SD=17.0) for controls. For the subsequent family-based study, the average age at assessment was 9.1 years (SD=2.8) for probands and 43 years (SD=7.9) for parents. Discovery cohort: Adulthood ADHD sample: The average age at diagnosis was 29.8 years (SD=12.1) for patients and 44.2 years (SD=14.7) for controls. Replication cohort: The average age at assessment was 10.74 years (SD=2.47) for probands.

Detail Info

Summary	We genotyped a total of 61 tagging single nucleotide polymorphisms (SNPs) in a sample of 533 ADHD patients (322 children and 211 adults), 533 sex-matched unrelated controls and additional 196 nuclear ADHD families from Spain. RESULTS: The single- and multiple-marker analysis in both population and family-based approaches provided preliminary evidence for the contribution of DRD1 to combined-type ADHD in children (P=8.8e-04; OR=1.50 (1.18-1.90) and P=0.0061; OR=1.73 (1.23-2.45)) but not in adults. Subsequently, we tested positive results for replication in an independent sample of 353 German families with combined-type ADHD children and replicated the initial association between DRD1 and childhood ADHD (P=8.4e-05; OR=3.67 (2.04-6.63)).
Total Sample	Discovery cohort: Childhood ADHD sample: Three hundred and twenty-two children with ADHD (73.6% combined, 21.7% inattentive and 4.7% hyperactive-impulsive) and 322 sex-matched unrelated controls. For the subsequent family-based study, one or both unscreened parents of a subset of 196 affected children suffering from combined-type ADHD, were available (both parents: n=137 and one parent: n=59). Discovery cohort: Adulthood ADHD sample: The adulthood population consisted of 211 ADHD subjects (140 combined, 61 inattentive and 10 hyperactiveimpulsive) and 211 sex-matched unrelated controls. Replication cohort: A total sample of 353 nuclear ADHD families from Germany (225 from the Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Wurzburg, and 128 from the Departments of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, and Neurobehavi oral Genetics, Institute of Psychobiology, Trier) with at least one child suffering from combined-type ADHD was assessed for replication.
Sample Collection	Discovery cohort: Childhood ADHD sample: recruited from two hospitals, Hospital Vall d'hebron and Hospital Mutua de Terrassa, located in the Barcelona area (Spain). Discovery cohort: Adulthood ADHD sample: recruited from Hospital Vall d'Hebron, Barcelona (Spain). Replication cohort: 225 from the Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Wurzburg, and 128 from the Departments of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg, and Neurobehavi oral Genetics, Institute of Psychobiology, Trier.
Diagnosis Description	Discovery cohort: Childhood ADHD sample: Patients were evaluated with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL) reported by parents. ADHD symptoms were assessed using the Conners' Parent Rating Scale and the Conners' Teacher Rating Scale. Discovery cohort: Adulthood ADHD sample: The ADHD diagnosis was based on the Structured Clinical Interview for DSM-IV Axis I and Axis II Disorders (SCID-I and SCID-II) and the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID). Replication cohort: All children were either assessed by the Kiddie-SADS-PL-German Version or the Kinder- DIPS, and parent and teacher ADHD DSM-IV based rating scales were obtained to ensure pervasiveness of symptoms.
Technique	All SNPs were genotyped using the SNPlex platform (Applied Biosystems, Foster City, CA, USA) as described (Tobler et al. 2005).
Analysis Method	The single- and multiple-marker analysis in both population and family-based approaches provided preliminary evidence for the contribution of DRD1 to combined-type ADHD in children (P=8.8e-04; OR=1.50 (1.18-1.90) and P=0.0061; OR=1.73 (1.23-2.45)) but not in adults. Subsequently, we tested positive results for replication in an independent sample of 353 German families with combined-type ADHD children and replicated the initial association between DRD1 and childhood ADHD (P=8.4e-05; OR=3.67 (2.04-6.63)). The replication of the association between DRD1 and ADHD in two European cohorts highlights the validity of our finding and supports the involvement of DRD1 in childhood ADHD.

SNPs reported by this study (count: 5)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2070762			children: genotypic P-value=0.062, genotype 11 vs 12+22: P-value=0.16, OR (95% CI)=-; genotype 11 +12 vs. 22: P-value=0.024, OR (95% CI)=1.65(1.06-2.55); allelic P-value=0.033, OR (95% CI)=1.28(1.02-1.59); adults: genotypic P-value=0.044, genotype 11 vs 12+22: P-value=0.09, OR (95% CI)=-; genotype 11 +12 vs. 22: P-value=0.24, OR (95% CI)=-; allelic P-value=0.55, OR (95% CI)=-	In the single-marker analysis the comparison of genotype fre...... In the single-marker analysis the comparison of genotype frequencies under a codominant model and allele frequencies showed nominal association between rs2070762 in the TH gene and both childhood and adulthood ADHD. More...	Significant
rs863126			genotypic P-value=0.0066, genotype 11 vs 12+22: P-value=0.016, OR (95% CI)=1.47 (1.07-2.0); genotype 11 +12 vs. 22: P-value=0.23, OR (95% CI)=-; allelic P-value=0.24, OR (95% CI)=-	Four SNPs in DRD1 displayed nominal associations with ADHD i...... Four SNPs in DRD1 displayed nominal associations with ADHD in the childhood dataset More...	Significant
rs265977			genotypic P-value=2.0E-04, genotype 11 vs 12+22: P-value=0.002, OR (95% CI)=1.72 (1.22-2.44); genotype 11 +12 vs. 22: P-value=7E-04, OR (95% CI)=7.69(1.75-33.3); allelic P-value=2.1E-04, OR (95% CI)=1.77(1.30-2.40)	Four SNPs in DRD1 displayed nominal associations with ADHD i...... Four SNPs in DRD1 displayed nominal associations with ADHD in the childhood dataset. After applying the Bonferroni correction, only rs265977 in DRD1 remained associated with ADHD in children More...	Significant
rs835541			genotypic P-value=0.011, genotype 11 vs 12+22: P-value=0.0043, OR (95% CI)=1.61 (1.16-2.27); genotype 11 +12 vs. 22: P-value=0.06, OR (95% CI)=-; allelic P-value=0.0026, OR (95% CI)=1.40 (1.12-1.75)	Four SNPs in DRD1 displayed nominal associations with ADHD i...... Four SNPs in DRD1 displayed nominal associations with ADHD in the childhood dataset More...	Significant
rs835616			genotypic P-value=0.026, genotype 11 vs 12+22: P-value=0.0072, OR (95% CI)=1.53 (1.12-2.09); genotype 11 +12 vs. 22: P-value=0.23, OR (95% CI)=-; allelic P-value=0.0086, OR (95% CI)=1.37 (1.09-1.75)	Four SNPs in DRD1 displayed nominal associations with ADHD i...... Four SNPs in DRD1 displayed nominal associations with ADHD in the childhood dataset More...	Significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DRD1	The single- and multiple-marker analysis in both population ...... The single- and multiple-marker analysis in both population and family-based approaches provided preliminary evidence for the contribution of DRD1 to combined-type ADHD in children (P=8.8e-04; OR=1.50 (1.18-1.90) and P=0.0061; OR=1.73 (1.23-2.45)) but not in adults. The replication of the association between DRD1 and ADHD in two European cohorts highlights the validity of our finding and supports the involvement of DRD1 in childhood ADHD. More...	Significant
TH	rs2070762 in the TH gene showed nominal association in both ...... rs2070762 in the TH gene showed nominal association in both childhood and adulthood ADHD. More...	Significant