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	Biederman J, 200818937309
Citation	Biederman J., Kim J. W., Doyle A. E., Mick E., Fagerness J., Smoller J. W. and Faraone S. V. (2008) "Sexually dimorphic effects of four genes (COMT, SLC6A2, MAOA, SLC6A4) in genetic associations of ADHD: a preliminary study." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1511-8.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	474 ADHD affected offspring
Predominant Ethnicity	Caucasian
Population	USA
Gender	308 males and 166 females
Age Group	Children/Adolescents and Adults : 2-39 years

Detail Info

Summary	They have investigated four ADHD candidate genes (COMT, SLC6A2, MAOA, SLC6A4) for which there is evidence of sexually dimorphic effects. Past neurobiological and genetic studies suggest that COMT, and SLC6A4 variants may have a greater influence on males and that SLC6A2, and MAOA variants may have a greater influence on females. Their results indicate that genetic associations are stronger when stratified by sex and in the same direction as the previous neurobiological studies indicate: associations were stronger in males for COMT, SLC6A4 and stronger in females for SLC6A2, MAOA. Moreover, they found a statistically significant gender effect in the case of COMT when they pooled their work with a prior study. In conclusion, they have found some evidence suggesting that the genetic association for these genes with ADHD may be influenced by the sex of the affected individual.
Total Sample	The final data set used in this study consisted of 474 ADHD affected offspring. Of those, 266 were probands and the remaining 208 were siblings who had ADHD. The age for the ADHD patients at the time of assessment ranged from 2 to 39 years. Three hundred sixty-one patients were children and 83 patients were adults at the time of assessment.
Sample Collection	The current analyses are derived from family studies of ADHD and bipolar disorder being conducted at the Massachusetts General Hospital. Additional sibling pairs with ADHD were ascertained from a family study of adults with ADHD.
Diagnosis Description	Initial affection status for individuals and their relatives was based on DSM-IIIR criteria; however lifetime DSM-IV criteria was asked at follow up interviews. For subjects of additional sibling pairs with ADHD, affection status was based on DSM-IV criteria for ADHD.
Technique	The genotyping for SNPs was performed using a multiple base extension reaction with allele discrimination by MassArray mass spectrometry system (BrUnited Kingdomer-Sequenom) as previously described [Sklar et al., 2002].
Analysis Method	The TDTPHASE program of the UNPHASED set [Dudbridge, 2003] was used for TDT analysis of transmission to each sex. They also tested whether there was a statistically significant difference between the transmissions to males vs. transmissions to females (gender effect) for each gene using a standard chi-square test with 1 degree of freedom. They converted each Chi-square value to z-scores, using a formula to examine the overall effect of the COMT Val158Met polymorphism in two independent samples including our families and another case¨Ccontrol study [Qian et al., 2003]
Result Description	Their results indicate that genetic associations are stronger when stratified by sex and in the same direction as the previous neurobiological studies indicate: associations were stronger in males for COMT, SLC6A4 and stronger in females for SLC6A2, MAOA. Moreover, the found a statistically significant gender effect in the case of COMT (P=0.007) when they pooled their work with a prior study.

SNPs reported by this study (count: 4)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2066713			TDT P-value=0.254 for all; TDT P-value=0.151 for transmission to male offspring; TDT P-value=1 for transmission to female offspring; TDT P-value=0.398, X²=0.71 for male versus female transmissions	they observed no evidence of association either in the full ...... they observed no evidence of association either in the full sample or when stratified by gender More...	Non-significant
rs3027399			TDT P-value=0.093 for all; TDT P-value=0.757 for transmission to male offspring; TDT P-value=0.021, OR=2.5 for transmission to female offspring; TDT P-value=0.111, X²=2.54 for male versus female transmissions	TDT analysis in the full sample was not significant and show...... TDT analysis in the full sample was not significant and showed a nominally significant effect for females but not for males More...	Significant
rs3785143			TDT P-value=0.02 for all; TDT P-value=0.37 for transmission to male offspring; TDT P-value=0.006, OR=2.11 for transmission to female offspring; TDT P-value=0.101, X²=2.68 for male versus female transmissions	TDT analysis in the full sample showed nominally significant...... TDT analysis in the full sample showed nominally significant association and the T allele of rs3785143 displayed a stronger effect in females than in males More...	Significant
rs4680			TDT P-value=0.023 for all; TDT P-value=0.003, OR=1.42 for transmission to male offspring; TDT P-value=0.936 for transmission to female offspring; TDT P-value=0.071, X²=3.27 for male versus female transmissions. P-value=0.007, Z=2.69 in pooled analysis of this study and a case-control study [Qian et al., 2003]	TDT analysis in the full sample showed nominally significant...... TDT analysis in the full sample showed nominally significant association and they observed overtransmission of the Met (A) allele to male offspring but not to female offspring; the pooled result showed a statistically significant gender effect for Val158Met in ADHD More...	Significant

Genes reported by this study (count: 4)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLC6A2	rs3785143 showed nominally significant association in the fu...... rs3785143 showed nominally significant association in the full sample and the T allele displayed a stronger effect in females than in males More...	Significant
MAOA	rs3027399 showed a nominally significant effect for females ...... rs3027399 showed a nominally significant effect for females but not for males More...	Significant
COMT	rs4680 showed overtransmission of the Met (A) allele to male...... rs4680 showed overtransmission of the Met (A) allele to male offspring but not to female offspring; the pooled result showed a statistically significant gender effect for Val158Met in ADHD More...	Significant
SLC6A4	no SNP showed evidence of association no SNP showed evidence of association	Non-significant