ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

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 ...

Meta-analysis Report

Basic Info

Reference	Gizer IR, 200919506906
Citation	Gizer I. R., Ficks C. and Waldman I. D. (2009) "Candidate gene studies of ADHD: a meta-analytic review." Hum Genet, 126(1): 51-90.
Study Type	Candidate association study
Summary	The first aim of the present study was to conduct a comprehensive meta-analytic review of this literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies. The second aim was to test for heterogeneity across studies in the effect sizes for each candidate gene as its presence might suggest moderating variables that could explain inconsistent results. Significant associations were identified for several candidate genes including DAT1, DRD4, DRD5, 5HTT, HTR1B, and SNAP25. Further, significant heterogeneity was observed for the associations between ADHD and DAT1, DRD4, DRD5, DBH, ADRA2A, 5HTT, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (e.g., ADHD subtype diagnoses, gender, exposure to environmental risk factors). They conclude with a discussion of these findings in relation to emerging themes relevant to future studies of the genetics of ADHD.

Detail Info

Samples	A four-stage approach was used to identify relevant studies for meta-analysis. After all relevant studies were identified, a series of inclusion and exclusion criteria were applied to determine which studies would be included in the meta-analysis for a given polymorphism. For detailed information, please refer to the original publication. Following the application of these inclusion/exclusion criteria, meta-analyses were performed for all polymorphisms for which usable data were reported in at least four published studies.
Statistic Method	Meta-analyses of TDT and Case-Control/HHRR studies were performed using the catmap package (version 1.6) in R (version 2.7.0). For TDT studies, odds ratios were estimated from the number of transmissions versus non-transmissions of the designated 'high-risk' allele to ADHD cases from heterozygous parents. For case-control studies, odds ratios were estimated by contrasting the ratio of counts of the 'high-risk' versus 'low-risk' alleles in ADHD cases versus non-disordered controls. Odds ratios for HHRR studies were estimated using a similar approach, in which the number of transmissions of the 'high-risk' and 'low-risk' alleles from both homozygous and heterozygous parents to ADHD cases was contrasted with the number of non-transmissions of the 'high-risk' and 'low-risk' alleles. Heterogeneity in effect sizes across studies was tested using the Q-statistic and its magnitude was quantified using I². Random effects meta-analyses were not performed in the absence of heterogeneity among study effect sizes. When a study reported results from both case-control and TDT analyses, data from the case-control analysis were included in the meta-analysis.
Basic Result	Several polymorphisms in candidate genes were associated with childhood ADHD, including several markers in the dopaminergic and serotonergic systems, and suggested associations in CHRNA4 and SNAP25. Heterogeneity in effect sizes across studies characterized several of the reviewed markers, including some that showed significant evidence for association and others that did not. This highlights the need for future studies that examine differences in sample and methodological characteristics that can explain such heterogeneity and point to ways of maximizing associations. Significant associations with candidate gene polymorphisms in this review were modest in magnitude, with Odds ratios ranging from 1.12 to 1.33.

SNPs reported by this study: 30

SNP	Statistical Values	Author Comments	Result of Statistical Analysis
rs6313	Meta-analysis model: Fixed: OR=0.96, 95% CI=0.86-1.06, two-tailed P-value=0.379; Q-statistic: P-value=0.644, I²=0	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs6311	Meta-analysis model: Fixed: OR=1.04, 95% CI=0.94-1.14, two-tailed P-value=0.449; Q-statistic: P-value=0.705, I²=0	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs6347	Meta-analysis model: Random: OR=1.08, 95% CI=0.94-1.22, two-tailed P-value=0.272; Q-statistic: P-value=0.325, I²=14	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs6314	Meta-analysis model: Random: OR=1.05, 95% CI=0.82-1.34, P-value=0.343; Q-statistic: P-value=0.121, I²=42	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1108580	Meta-analysis model: Random: OR=1.09, 95% CI=0.93-1.28, P-value=0.145; Q-statistic: P-value=0.284, I²=20	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1051312	Meta-analysis model: Random: OR=1.06, 95% CI=0.86-1.31, P-value=0.298; Q-statistic: P-value=0.084, I²=48	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1800532	Meta-analysis model: Random: OR=0.97, 95% CI=0.83-1.12, two-tailed P-value=0.662; Q-statistic: P-value=0.164, I²=41	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1800497	Meta-analysis model: Random: OR=1.65, 95% CI=0.89-3.06, two-tailed P-value=0.11; Q-statistic: P-value=0.000001, I²=91	The results of the meta-analysis were statistically mixed. D...... The results of the meta-analysis were statistically mixed. Due to the magnitude of the observed heterogeneity, it is difficult to draw definitive conclusions regarding the association between childhood ADHD and the polymorphisms/gene. More...	Significant
rs1611115	Meta-analysis model: Random: OR=1.05, 95% CI=0.83-1.33, two-tailed P-value=0.692; Q-statistic: P-value=0.189, I²=37	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1386493	Meta-analysis model: Random: OR=1.04, 95% CI=0.77-1.40, P-value=0.4; Q-statistic: P-value=0.021, I²=69	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1843809	Meta-analysis model: Random: OR=1.15, 95% CI=0.73-1.82, P-value=0.276; Q-statistic: P-value=0.0002, I²=84	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1800955	Meta-analysis model: Fixed: OR=1.21, 95% CI=1.04-1.41, P-value=0.007; Q-statistic: P-value=0.472, I²=0	significant but modest association significant but modest association	Significant
rs1800545	Meta-analysis model: Fixed: OR=0.99, 95% CI=0.81-1.21, two-tailed P-value=0.914; Q-statistic: P-value=0.67, I²=0	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs1800544	Meta-analysis model: Random: OR=0.99, 95% CI=0.89-1.11, P-value=0.542; Q-statistic: P-value=0.272, I²=18	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs2519152	Meta-analysis model: Random: OR=1.12, 95% CI=0.80-1.55, P-value=0.206; Q-statistic: P-value=0.004, I²=71	The results of the meta-analysis were statistically mixed. D...... The results of the meta-analysis were statistically mixed. Due to the magnitude of the observed heterogeneity, it is difficult to draw definitive conclusions regarding the association between childhood ADHD and the polymorphisms/gene. More...	Non-significant
rs27072	Meta-analysis model: Random: OR=1.2, 95% CI=1.04-1.38, P-value=0.006; Q-statistic: P-value=0.217, I²=28	significant but modest association significant but modest association	Significant
rs2242447	Meta-analysis model: Random: OR=1.04, 95% CI=0.91-1.19, two-tailed P-value=0.589; Q-statistic: P-value=0.319, I²=14	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs2273506	Meta-analysis model: Fixed: OR=1.19, 95% CI=0.92-1.54, P-value=0.089; Q-statistic: P-value=0.504, I²=0	The results suggested a trend towards an association with AD...... The results suggested a trend towards an association with ADHD. There was no significant evidence of heterogeneity in effect sizes across studies. A sensitivity analysis indicated that the trend for an association between ADHD and rs2273506 was largely driven by a single study (Todd et al. 2003), as removal of this study reduced the trend towards association to nonsignificance. More...	Non-significant
rs3746544	Meta-analysis model: Fixed: OR=1.15, 95% CI=1.01-1.31, two-tailed P-value=0.03; Q-statistic: P-value=0.847, I²=0	significant but modest association significant but modest association	Significant
rs3813034	Meta-analysis model: Random: OR=1.05, 95% CI=0.87-1.26, P-value=0.304; Q-statistic: P-value=0.222, I²=30	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs362987	Meta-analysis model: Random: OR=1, 95% CI=0.84-1.18, P-value=0.488; Q-statistic: P-value=0.099, I²=49	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs363006	Meta-analysis model: Random: OR=0.99, 95% CI=0.86-1.15, P-value=0.547; Q-statistic: P-value=0.326, I²=14	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs553668	Meta-analysis model: Random: OR=0.94, 95% CI=0.66-1.34, P-value=0.638; Q-statistic: P-value=0.044, I²=63	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs5569	Meta-analysis model: Fixed: OR=1.06, 95% CI=0.95-1.18, two-tailed P-value=0.279; Q-statistic: P-value=0.992, I²=0	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs40184	Meta-analysis model: Random: OR=1.06, 95% CI=0.90-1.24, P-value=0.249; Q-statistic: P-value=0.141, I²=45	The Fixed effects meta-analysis indicated a trend towards a ...... The Fixed effects meta-analysis indicated a trend towards a modest association between this allele and ADHD, but random effects meta-analysis yielded a nonsignificant result. Moderate but non-significant heterogeneity in effect sizes across studies was observed. An important caveat to these findings is that the results are based on only 4 studies. More...	Non-significant
rs4680	Meta-analysis model: Random: OR=0.99, 95% CI=0.91-1.08, P-value=0.575; Q-statistic: P-value=0.287, I²=15	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs6280	Meta-analysis model: Fixed: OR=1.07, 95% CI=0.95-1.21, two-tailed P-value=0.268; Q-statistic: P-value=0.952, I²=0	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant
rs6296	Meta-analysis model: Fixed: OR=1.11, 95% CI=1.02-1.20, P-value=0.01; Q-statistic: P-value=0.441, I²=0	significant but modest association significant but modest association	Significant
rs6090384	Meta-analysis model: Random: OR=1.28, 95% CI=0.89-1.84, P-value=0.093; Q-statistic: P-value=0.271, I²=23	The results of this meta-analysis also suggested a trend tow...... The results of this meta-analysis also suggested a trend towards association with childhood ADHD with no significant evidence of heterogeneity in effect sizes across studies. Sensitivity analyses indicated this association reached significance after removing the Brookes et al. (2006a) study, though removing any of the other studies reduced the trend to non-significance. It is likely that the fluctuations in the significance of this association observed in the sensitivity analyses were influenced by the small number of studies included in the meta-analysis. More...	Non-significant
rs6265	Meta-analysis model: Fixed: OR=1.01, 95% CI=0.91-1.12, P-value=0.406; Q-statistic: P-value=0.504, I²=0	no evidence to suggest an association between this polymorph...... no evidence to suggest an association between this polymorphisms and ADHD More...	Non-significant

Genes reported by this study: 18

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
TPH1	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
SLC6A3	The present study provides significant evidence suggesting a...... The present study provides significant evidence suggesting an association between childhood ADHD and this gene. More...	Significant
DRD3	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
SLC6A2	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
HTR1B	The present study provides significant evidence suggesting a...... The present study provides significant evidence suggesting an association between childhood ADHD and this gene. More...	Significant
BDNF	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
MAOA	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
SLC6A4	The present study provides significant evidence of an associ...... The present study provides significant evidence of an association between ADHD and the 5HTTLPR, but failed to detect an association with the STin2 and rs3813034 polymorphisms. More...	Significant
DRD2	The results of the meta-analysis were statistically mixedDue...... The results of the meta-analysis were statistically mixedDue to the magnitude of the observed heterogeneity, it is difficult to draw definitive conclusions regarding the association between childhood ADHD and the polymorphisms/gene. More...	Significant
SNAP25	The 3' UTR SNP rs3746544 yielded evidence of a modest but si...... The 3' UTR SNP rs3746544 yielded evidence of a modest but significant association between childhood ADHD and SNAP-25. More...	Significant
ADRA2A	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
DBH	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
DRD5	The present study provides significant evidence suggesting a...... The present study provides significant evidence suggesting an association between childhood ADHD and this gene. More...	Significant
CHRNA4	The present review suggests a possible association between c...... The present review suggests a possible association between childhood ADHD and CHRNA4. More...	Non-significant
HTR2A	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
TPH2	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
COMT	The present study does not support a relation between ADHD a...... The present study does not support a relation between ADHD and this gene. More...	Non-significant
DRD4	The present study provides significant evidence suggesting a...... The present study provides significant evidence suggesting an association between childhood ADHD and this gene. More...	Significant