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	Sanchez-Mora, C., 201222939005
Citation	Sanchez-Mora C., Cormand B., Ramos-Quiroga J. A., Hervas A., Bosch R., Palomar G., Nogueira M., Gomez-Barros N., Richarte V., Corrales M., Garcia-Martinez I., Corominas R., Guijarro S., Bigorra A., Bayes M., Casas M. and Ribases M. (2012) "Evaluation of common variants in 16 genes involved in the regulation of neurotransmitter release in ADHD." Eur Neuropsychopharmacol.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	506 adulthood ADHD and 444 childhood ADHD
Predominant Ethnicity	Caucasian
Population	Spanish
Age Group	Children/Adolescents and Adults : The average age at assessment was 30.2 years (SD=12.1) for adult patients, 9.3 years (SD=2.6) for child patients, and 39.9 years (SD=17.0) for control subjects.

Detail Info

Summary	With this background, we evaluated, both in childhood and adulthood ADHD, the role of several genes involved in the control of neurotransmitter release through synaptic vesicle docking, fusion and recycling processes by means of a population-based association study. We analyzed single nucleotide polymorphisms across 16 genes in a clinical sample of 950 ADHD patients (506 adults and 444 children) and 905 controls. Single and multiple-marker analyses identified several significant associations after correcting for multiple testing with a false discovery rate (FDR) of 15%: (i) the SYT2 gene was strongly associated with both adulthood and childhood ADHD (p=0.001, OR=1.49 (1.18-1.89) and p=0.007, OR=1.37 (1.09-1.72), respectively) and (ii) STX1A was found associated with ADHD only in adults (p=0.0041; OR=1.28 (1.08-1.51)).
Total Sample	506 adulthood ADHD (63.6% combined, 32.6% inattentive and 3.5% hyperactive-impulsive) and 444 childhood ADHD (70.3% combined, 24.7% inattentive and 4.3% hyperactive-impulsive)
Sample Collection	patients of Caucasian origin from Spain were recruited and evaluated at Hospital Universitari Valld Hebronandat Hospital Universitari Mutua de Terrassa, located in the Barcelona area (Spain).
Diagnosis Description	All subjects met DSM-IV criteria for ADHD. The diagnosis of ADHD in adulthood was evaluated with the Structured Clinical Interview for DSM-IV Axis I and II Disorders(SCID-IandSCID-II) and the Conners' Adult ADHD Diagnostic Interview for DSM-IV. The diagnosis of ADHD in children was evaluated with the present and life time version of the Schedule for Affective Disorders and Schizophrenia for School-age children (K-SADS-PL).
Technique	SNPs were genotyped using the Illumina Bead Xpress plata form and the Golden Gate Genotyping Assay (Illumina,SanDiego,CA,USA).
Analysis Method	Single-markeranalysis: The analysis of Hardy-Weinberg equilibrium in the control sample (threshold set at p<0.01) and the comparison of genotype and allele frequencies between cases and controls were performed using the SNP assocR package. Multiple-marker analysis: Significance was estimated by a permutation procedure using 10,000 permutations with the UNPHASED software. Estimated haplotypes were assigned to individuals with the PHASE2.0 software. The frequency of risk haplotype carriers was compared between cases and controls usinga X2 test with the SPSS15.0 statistical package.
Result Description	Single and multiple-marker analyses identified several significant associations after correcting for multiple testing with a false discovery rate (FDR) of 15%: (i) the SYT2 gene was strongly associated with both adulthood and childhood ADHD (p=0.001, OR=1.49 (1.18-1.89) and p=0.007, OR=1.37 (1.09-1.72), respectively) and (ii) STX1A was found associated with ADHD only in adults (p=0.0041; OR=1.28 (1.08-1.51)). These data provide preliminary evidence for the involvement of genes that participate in the control of neurotransmitter release in the genetic predisposition to ADHD through a gene-system association study. Further follow-up studies in larger cohorts and deep-sequencing of the associated genomic regions are required to identify sequence variants directly involved in ADHD.

SNPs reported by this study (count: 18)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2114968			P-value=0.058, Genotype12+22 vs11: P-value=0.017, OR(95%CI)=1.35(1.05¨C1.72); Genotypes22 vs11+12: P-value=0.528, OR(95%CI)=1.09(0.81¨C1.493); allelic P-value=0,050, OR(95%CI)=1.17(1¨C1.38)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. More...	Significant
rs10503024			P-value=0.118, Genotype12+22 vs11: P-value=0.059, OR(95%CI)=1.23(0.99¨C1.53); Genotypes22 vs11+12: P-value=0.155, OR(95%CI)=1.29(0.90¨C1.85); allelic P-value=0,036, OR(95%CI)=1.19(1.01¨C1.41)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. More...	Significant
rs640401			P-value=0.008, Genotype12+22 vs11: P-value=0.028, OR(95%CI)=1.30(1.03¨C1.64); Genotypes22 vs11+12: P-value=0.36, OR(95%CI)=1.28(0.75¨C2.17); allelic P-value=0,027, OR(95%CI)=1.25(1.02¨C1.54)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. More...	Significant
rs2251214			P-value=0.116, Genotype12+22 vs11: P-value=0.114, OR(95%CI)=1.19(0.96¨C1.49); Genotypes22 vs11+12: P-value=0.077, OR(95%CI)=1.52(0.94¨C2.38); allelic P-value=0,044, OR(95%CI)=1.20(1¨C1.45)	"When adults with ADHD were considered, nominal differences ...... "When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. " More...	Significant
rs2228607			P-value=0.002, Genotype12+22 vs11: P-value=0.008, OR(95%CI)=1.39(1.09¨C1.77); Genotypes22 vs11+12: P-value=0.002, OR(95%CI)=1.52(1.17¨C1.98); allelic P-value=4.2e-04, OR(95%CI)=1.32(1.13¨C1.54)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. After applying a FDR of 15%, only the four SNPs in STX1A remained associated with adulthood ADHD. More...	Significant
rs3793243			P-value=0.003, Genotype12+22 vs11: P-value=0.006, OR(95%CI)=1.39(1.10¨C1.77); Genotypes22 vs11+12: P-value=0.006, OR(95%CI)=1.46(1.12¨C1.92); allelic P-value=7.1e-4, OR(95%CI)=1.31(1.12¨C1.53)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. After applying a FDR of 15%, only the four SNPs in STX1A remained associated with adulthood ADHD. More...	Significant
rs4363087			P-value=0.003, Genotype12+22 vs11: P-value=0.001, OR(95%CI)=1.44(1.15¨C1.80); Genotypes22 vs11+12: P-value=0.021, OR(95%CI)=1.45(1.06¨C1.98); allelic P-value=5.6e-04, OR(95%CI)=1.31(1.12¨C1.56)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. After applying a FDR of 15%, only the four SNPs in STX1A remained associated with adulthood ADHD. More...	Significant
rs6832751			P-value=0.138, Genotype12+22 vs11: P-value=0.050, OR(95%CI)=1.25(1.0¨C1.56); Genotypes22 vs11+12: P-value=0.339, OR(95%CI)=1.19(0.95¨C1.49); allelic P-value=0,049, OR(95%CI)=1.2(1.0¨C1.43)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. More...	Significant
rs941298			P-value=0.012, Genotype12+22 vs11: P-value=0.012, OR(95%CI)=1.32(1.06¨C1.65); Genotypes22 vs11+12: P-value=0.020, OR(95%CI)=1.52(1.07¨C2.17); allelic P-value=0.003, OR(95%CI)=1.29(1.09¨C1.52)	When adults with ADHD were considered, nominal differences w...... When adults with ADHD were considered, nominal differences were found for nine SNPs located in five genes. After applying a FDR of 15%, only the four SNPs in STX1A remained associated with adulthood ADHD. More...	Significant
rs6539445			P-value=0.008, Genotype12+22 vs11: P-value=0.020, OR(95%CI)=1.35(1.05¨C1.75); Genotypes22 vs11+12: P-value=0.010, OR(95%CI)=2.89(1.27¨C6.57); allelic P-value=0,005, OR(95%CI)=1.37(1.10¨C1.72)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs6134520			P-value=0.069, Genotype12+22 vs11: P-value=0.034, OR(95%CI)=1.28(0.62¨C0.98); Genotypes22 vs11+12: P-value=0.135, OR(95%CI)=1.36(0.89¨C2.12); allelic P-value=0,024, OR(95%CI)=1.22(1.03¨C1.46)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs3764715			P-value=0.110, Genotype12+22 vs11: P-value=0.041, OR(95%CI)=1.26(1.01¨C1.59); Genotypes22 vs11+12: P-value=0.290, OR(95%CI)=1.13(0.82¨C1.92); allelic P-value=0,043, OR(95%CI)=1.20(1¨C1.43)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs11134942			P-value=0.019, Genotype12+22 vs11: P-value=0.008, OR(95%CI)=1.37(1.08¨C1.75); Genotypes22 vs11+12: P-value=0.992, OR(95%CI)=1.0(0.73¨C1.38); allelic P-value=0,062, OR(95%CI)=1.17(0.99¨C1.39)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs3733358			P-value=0.009, Genotype12+22 vs11: P-value=0.609, OR(95%CI)=1.06(0.84¨C1.35); Genotypes22 vs11+12: P-value=0.006, OR(95%CI)=1.78(1.14¨C2.70); allelic P-value=0,403, OR(95%CI)=1.07(0.90¨C1.30)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs907697			P-value=0.008, Genotype12+22 vs11: P-value=0.0045, OR(95%CI)=1.45(1.12¨C1.89); Genotypes22 vs11+12: P-value=0.040, OR(95%CI)=1.34(1.01¨C1.78); allelic P-value=0,003, OR(95%CI)=1.28(1.09¨C1.51)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs12739678			P-value=0.097, Genotype12+22 vs11: P-value=0.070, OR(95%CI)=1.24(0.98¨C1.56); Genotypes22 vs11+12: P-value=0.105, OR(95%CI)=1.46(0.93¨C2.29); allelic P-value=0,040, OR(95%CI)=1.20(1.01¨C1.45)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs6427957			P-value=0.016, Genotype12+22 vs11: P-value=0.004, OR(95%CI)=1.47(1.13¨C1.92); Genotypes22 vs11+12: P-value=0.309, OR(95%CI)=1.15(0.88¨C1.52); allelic P-value=0,017, OR(95%CI)=1.22(1.04¨C1.43)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant
rs9633344			P-value=0.059, Genotype12+22vs11: P-value=0.022, OR(95%CI)=1.32(1.04¨C1.69); Genotypes22vs11+12: P-value=0.184, OR(95%CI)=1.24(0.90¨C1.70); allelic P-value=0,025, OR(95%CI)=1.21(1.02¨C1.42)	Nine SNPs located in five genes displayed nominal associatio...... Nine SNPs located in five genes displayed nominal associations in the comparison of ADHD children and controls More...	Significant

Genes reported by this study (count: 7)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
STX1A	STX1A was found associated with ADHD only in adults (p=0.004...... STX1A was found associated with ADHD only in adults (p=0.0041; OR=1.28 (1.08-1.51)) More...	Significant
SYT1	nominal differences were found with both adulthood ADHD and ...... nominal differences were found with both adulthood ADHD and children ADHD. More...	Significant
CPLX1	nominal differences were found with both adulthood ADHD and ...... nominal differences were found with both adulthood ADHD and children ADHD. More...	Significant
SYT2	the SYT2 gene was strongly associated with both adulthood an...... the SYT2 gene was strongly associated with both adulthood and childhood ADHD (p=0.001, OR=1.49 (1.18-1.89) and p=0.007, OR=1.37 (1.09-1.72), respectively) More...	Significant
CPLX2	nominal differences were found with adulthood ADHD. nominal differences were found with adulthood ADHD.	Significant
SNPH	nominal differences were found with children ADHD. nominal differences were found with children ADHD.	Significant
CPLX4	nominal differences were found with adulthood ADHD. nominal differences were found with adulthood ADHD.	Significant