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

Detail ...

Study Report

Basic Info

Reference	Guan L, 200918180757
Citation	Guan L., Wang B., Chen Y., Yang L., Li J., Qian Q., Wang Z., Faraone S. V. and Wang Y. (2009) "A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population." Mol Psychiatry, 14(5): 546-54.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	182 cases and 184 controls
Predominant Ethnicity	Mongoloid
Population	China
Gender	153 males and 29 female in case group; 145 males and 39 females in control group
Age Group	Children/Adolescents : aged 6-16; mean age 9.8 years (SD=2.6) in case group, mean age 23.0 years (median) in control group.

Detail Info

Summary	In this study, they emphasized genes that underlie various aspects of dopamine, norepinephrine and serotonin neurotransmissions and performed a comprehensive association analysis by screening with 245 SNPs of 23 candidate genes in a sample of Chinese Han descent. A total of 182 DSM-IV ADHD children and 184 healthy controls were genotyped and analyzed with an average density of one SNP every 6.1 kb. Both single-SNP and multimarker haplotype analyses were implemented to exploit association signal for ADHD and its diagnostic subtypes. Empirical P-values were derived on the basis of 5000 permutations to evaluate gene-wide statistical significance. MAOA yielded highly suggestive evidence of association (empirical P-value<0.01, OR=1.94) with ADHD. For inattentive ADHD, MAOA, DDC and SYP showed suggestive evidence of association (empirical P-value<0.05). ADRA2C achieved suggestive significance (empirical P-value<0.05) for ADHD combined type. Additionally, for six genes (SNAP25, NET1, DBH, CHRNA4, DRD3 and SYT1) they detected one or more SNPs with nominal P-values<=0.05. This study has identified several genes as promising susceptibility loci for ADHD. Replication efforts and further investigations remain necessary to provide definite proof of association.
Total Sample	184 cases and 184 controls were recruited. After QC, the final data set comprised 182 ADHD children and 184 healthy individuals.
Sample Collection	ADHD youths were recruited from child psychiatric clinics of the Institute of Mental Health, Peking University from June 2004 to December 2005. Normal controls were ascertained from healthy blood donors from the Blood Center of the First Hospital, Peking University and from healthy volunteers at our Institute. All were of Chinese Han descent.
Diagnosis Description	Eligible cases for recruiting in the study met inclusion criteria as follows: (1) met DSM-IV ADHD diagnostic criteria, (2) age between 6 and 16 years, (3) full-scale estimated IQ > 70 and (4) both biological parents were of Chinese Han descent. Individuals with major neurological handicaps, a diagnosis of schizophrenia, pervasive development disorder, epilepsy, mental retardation or other brain disorders were excluded. The exclusion criteria for controls were ADHD, other major psychiatric disorders, family history of psychosis, severe physical diseases and substance abuse.
Technique	Genomic DNA was extracted directly from blood using the standard protocols (Omega Bio-tek Inc., Doraville, GA, USA). Each sample was genotyped at a multiplex level of 384 SNPs per well on a custom array using the Illumina highthroughput BeadArray technology. The assay products were hybridized to high-density, bead-based microarrays. The fluorescence signal generated from each genotype was imaged on a submicron-resolution scanner to produce genotypes.
Analysis Method	Hardy-Weinberg equilibrium (HWE) was assessed by using HAPLOVIEW version 3.32 on the control group. Association with DSM-IV ADHD and its diagnostic subtypes are tested respectively. Both single-SNP and multi-marker haplotype association analyses were implemented in HAPLOVIEW. For single-marker tests of association, the X² and nominal P-value for the allele frequencies in case vs. control were obtained. A total of 5000 permutations were performed to empirically estimate significance levels to correct for multiple testing bias at the genewide level. For X-chromosome genes, they calculated haplotype associations by running X² tests in SPSS 13.0 with the use of the haplotype estimates created by HAPLOVIEW version 3.2. The significance values of X-chromosome haplotypes were adjusted by using the Bonferroni correction. For detailed information, please refer to the original publication.
Result Description	Single SNP analyses: Ten genes contained one or more SNP that was nominally significant. Haplotype analyses: Nominal evidence of association for SNAP25 and DDC in ADHD; DDC , SNAP25, CHRNA4 and DBH in ADHD-I; SNAP25, DBH and DRD3 in ADHD-C were found. All these associated haplotypes contained SNPs that were nominally significant in single-marker tests. After permutation tests were implemented, no significant association was identifiable except that DDC reached marginal significance with an empirical P-value of 0.052 (OR = 1.68) for inattentive subtype ADHD.

SNPs reported by this study (count: 36)

SNP	Statistical Values	Author Comments	Result of Statistical Analysis
rs10861968	single SNP association analyses: Nominal P-value=0.046, Empirical P-value=0.274 for ADHD-C	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-C More...	Significant
rs1076150	single SNP association analyses: Nominal P-value=0.027, Empirical P-value=0.386 for ADHD-C	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-C More...	Significant
rs1137070	single SNP association analyses: Nominal P-value=0.012, Empirical P-value=0.017 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs1108580	single SNP association analyses: Nominal P-value=0.033, Empirical P-value=0.433 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs2072744	single SNP association analyses: Nominal P-value=0.012, Empirical P-value=0.017 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs1548364	single SNP association analyses: Nominal P-value=0.05, Empirical P-value=0.566 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Non-significant
rs2235186	single SNP association analyses: Nominal P-value=0.012, Empirical P-value=0.017 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs2235185	single SNP association analyses: Nominal P-value=0.012, Empirical P-value=0.017 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs1349492	single SNP association analyses: Nominal P-value=0.025, Empirical P-value=0.206 for ADHD; Nominal P-value=0.006, Empirical P-value=0.052 for ADHD-I	achieve nominal significance for ADHD and ADHD-I achieve nominal significance for ADHD and ADHD-I	Significant
rs12843268	single SNP association analyses: Nominal P-value=0.006, Empirical P-value=0.008 for ADHD; Nominal P-value=0.01, Empirical P-value=0.018 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs1470750	single SNP association analyses: Nominal P-value=0.047, Empirical P-value=0.361 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs1451371	single SNP association analyses: Nominal P-value=0.036, Empirical P-value=0.276 for ADHD; Nominal P-value=0.012, Empirical P-value=0.116 for ADHD-I	achieve nominal significance for ADHD and ADHD-I achieve nominal significance for ADHD and ADHD-I	Significant
rs3027400	single SNP association analyses: Nominal P-value=0.009, Empirical P-value=0.012 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs3027407	single SNP association analyses: Nominal P-value=0.012, Empirical P-value=0.017 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs36009	single SNP association analyses: Nominal P-value=0.018, Empirical P-value=0.267 for ADHD-C	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-C More...	Significant
rs362988	single SNP association analyses: Nominal P-value=0.033, Empirical P-value=0.505 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs2239448	single SNP association analyses: Nominal P-value=0.012, Empirical P-value=0.017 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs2327265	single SNP association analyses: Nominal P-value=0.034, Empirical P-value=0.528 for ADHD-C	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-C More...	Significant
rs2519154	single SNP association analyses: Nominal P-value=0.024, Empirical P-value=0.37 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs2873804	single SNP association analyses: Nominal P-value=0.05, Empirical P-value=0.566 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Non-significant
rs5905859	single SNP association analyses: Nominal P-value=0.009, Empirical P-value=0.012 for ADHD; Nominal P-value=0.018, Empirical P-value=0.034 for ADHD-I	achieve nominal and empirical significance for ADHD and ADHD...... achieve nominal and empirical significance for ADHD and ADHD-I More...	Significant
rs5906754	single SNP association analyses: Nominal P-value=0.045, Empirical P-value=0.048 for ADHD-I	non-significant for ADHD, but achieve nominal and empirical ...... non-significant for ADHD, but achieve nominal and empirical significance for ADHD-I More...	Significant
rs5953210	single SNP association analyses: Nominal P-value=0.031, Empirical P-value=0.051 for ADHD; Nominal P-value=0.036, Empirical P-value=0.052 for ADHD-I	achieve nominal significance for ADHD and ADHD-I achieve nominal significance for ADHD and ADHD-I	Significant
rs6108464	single SNP association analyses: Nominal P-value=0.007, Empirical P-value=0.151 for ADHD; Nominal P-value=0.003, Empirical P-value=0.066 for ADHD-C	achieve nominal significance for ADHD and ADHD-C, also empir...... achieve nominal significance for ADHD and ADHD-C, also empirical significante for ADHD-C More...	Significant
rs3788863	single SNP association analyses: Nominal P-value=0.031, Empirical P-value=0.051 for ADHD; Nominal P-value=0.036, Empirical P-value=0.052 for ADHD-I	achieve nominal significance for ADHD and ADHD-I achieve nominal significance for ADHD and ADHD-I	Significant
rs3818204	single SNP association analyses: Nominal P-value=0.025, Empirical P-value=0.152 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs4570308	single SNP association analyses: Nominal P-value=0.031, Empirical P-value=0.051 for ADHD; Nominal P-value=0.036, Empirical P-value=0.052 for ADHD-I	achieve nominal significance for ADHD and ADHD-I achieve nominal significance for ADHD and ADHD-I	Significant
rs4813925	single SNP association analyses: Nominal P-value=0.043, Empirical P-value=0.703 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs998850	single SNP association analyses: Nominal P-value=0.032, Empirical P-value=0.255 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs8636	single SNP association analyses: Nominal P-value=0.032, Empirical P-value=0.491 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs7682295	single SNP association analyses: Nominal P-value=0.036, Empirical P-value=0.105 for ADHD \| Nominal P-value=0.011, Empirical P-value=0.042 for ADHD-C	achieve nominal significance for ADHD and ADHD-C, also empir...... achieve nominal significance for ADHD and ADHD-C, also empirical significante for ADHD-C More...	Significant
rs7638876	single SNP association analyses: Nominal P-value=0.037, Empirical P-value=0.293 for ADHD-C	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-C More...	Significant
rs755203	single SNP association analyses: Nominal P-value=0.032, Empirical P-value=0.19 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs732215	single SNP association analyses: Nominal P-value=0.014, Empirical P-value=0.127 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs7315638	single SNP association analyses: Nominal P-value=0.044, Empirical P-value=0.299 for ADHD-I	non-significant for ADHD, but achieve nominal significance f...... non-significant for ADHD, but achieve nominal significance for ADHD-I More...	Significant
rs6592952	single SNP association analyses: Nominal P-value=0.003, Empirical P-value=0.032 for ADHD-I	non-significant for ADHD, but achieve nominal and empirical ...... non-significant for ADHD, but achieve nominal and empirical significance for ADHD-I More...	Significant

Genes reported by this study (count: 10)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DDC	haplotype association analysis: Nominal P-value=0.031, Empir...... haplotype association analysis: Nominal P-value=0.031, Empirical P-value=0.26 for ADHD \| Nominal P-value=0.006, Empirical P-value=0.052 for ADHD-I. 6 SNPs in this gene achieved nominal significance for ADHD/ADHD-I, and haplotype association test also achieved nominal significance for ADHD/ADHD-I. More...	Significant
DBH	haplotype association analysis: Nominal P-value=0.041, Empir...... haplotype association analysis: Nominal P-value=0.041, Empirical P-value=0.509 for ADHD-I; Nominal P-value=0.035, Empirical P-value=0.419 for ADHD-C. 5 SNPs in this gene achieved nominal significance for ADHD-I/ADHD-C, and haplotype association test also achieved nominal significance for ADHD-I/ADHD-C. More...	Significant
MAOA	haplotype association analysis: P-value=0.023 for ADHD and 0...... haplotype association analysis: P-value=0.023 for ADHD and 0.024 for ADHD-I under individual test, P-value=0.019 for ADHD and 0.011 for ADHD-I under global test. 12 SNPs in this gene achieved significance for ADHD and ADHD-I, and haplotype association test also achieved significance for ADHD and ADHD-I unber both individual and global test. More...	Significant
DRD3	haplotype association analysis: Nominal P-value=0.037, Empir...... haplotype association analysis: Nominal P-value=0.037, Empirical P-value=0.293 for ADHD-C. 1 SNP in this gene achieved nominal significance for ADHD-C, and haplotype association test also achieved nominal significance for ADHD-C. More...	Significant
SNAP25	haplotype association analysis: Nominal P-value=0.021, Empir...... haplotype association analysis: Nominal P-value=0.021, Empirical P-value=0.378 for ADHD \| Nominal P-value=0.032, Empirical P-value=0.491 for ADHD-I \| Nominal P-value=0.023, Empirical P-value=0.396 for ADHD-C. 5 SNPs in this gene achieved nominal significance for ADHD/ADHD-I/ADHD-C, and haplotype association test also achieved nominal significance for ADHD and both of subtypes. More...	Significant
SLC6A2	1 SNP in this gene achieved significance for ADHD-C in singl...... 1 SNP in this gene achieved significance for ADHD-C in single SNP association analysis. More...	Significant
ADRA2C	1 SNP in this gene achieved significance for ADHD and ADHD-C...... 1 SNP in this gene achieved significance for ADHD and ADHD-C in single SNP association analysis. More...	Significant
SYT1	2 SNPs in this gene achieved significance for ADHD-I and ADH...... 2 SNPs in this gene achieved significance for ADHD-I and ADHD-C respectively in single SNP association analysis. More...	Significant
SYP	1 SNP in this gene achieved significance for ADHD-I in singl...... 1 SNP in this gene achieved significance for ADHD-I in single SNP association analysis. More...	Significant
CHRNA4	haplotype association analysis: Nominal P-value=0.037, Empir...... haplotype association analysis: Nominal P-value=0.037, Empirical P-value=0.224 for ADHD-I. 2 SNPs in this gene achieved significance for ADHD-I, and haplotype association test also achieved significance for ADHD-I. More...	Significant