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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	Liu, L., 201121761555
Citation	Liu L., Guan L. L., Chen Y., Ji N., Li H. M., Li Z. H., Qian Q. J., Yang L., Glatt S. J., Faraone S. V. and Wang Y. F. (2011) "Association analyses of MAOA in Chinese Han subjects with attention-deficit/hyperactivity disorder: family-based association test, case-control study, and quantitative traits of impulsivity." Am J Med Genet B Neuropsychiatr Genet, 156B(6): 737-48.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	1840 cases including 1,269 probands with parents and 957 controls
Predominant Ethnicity	Mongloid
Population	Chinese
Gender	1517 (83.2%) male patients, 1050 (83.8%) males in trio subsample and 617 (64.5%) controls
Age Group	Children/Adolescents and Adults : Mean age in months=121.25, SD=31 of ADHD whole, mean age in months=119.33 (SD=30.7) of ADHD trio subsample; mean age in months=185.31 (SD=102.0) of controls

Detail Info

Summary	We conducted transmission disequilibrium tests (TDTs) in 1,253 trios and found no association between five single nucleotide polymorphisms (SNPs) of MAOA with ADHD in general or in the predominantly inattentive (ADHD-I) or combined types (ADHD-C), but with the predominantly hyperactive/impulsivity type (ADHD-HI). The association with MAOA was restricted to males, especially males with ADHD-HI. Logistic regression analyses of data from 1,824 cases and 957 controls did not indicate any association. We used analysis of covariance to analyze the association between MAOA genotype with the "inhibit" factor of the Behavior Rating Inventory of Executive Function (BRIEF) in 640 probands and performance on the Stroop test in 810 probands. Probands homozygous for risk alleles found in the TDT test had higher "inhibit" scores on the BRIEF scale which represents more severe impulsivity; this results also was restricted to males. No association was found with Stroop test performance.
Total Sample	This sample comprised 1,840 ADHD cases recruited from child psychiatric clinics of Peking University Institute of Mental Health. Among these cases there were 1,269 probands who, along with their parents, constituted trios to be included for the analyses of familybased association. Nine hundred fifty seven non-mentally ill control subjects were ascertained from local elementary schools, healthy blood donors from the Blood Center of the First Hospital, Peking University, and from healthy volunteers at our Institute.
Sample Collection	This sample comprised 1,840 ADHD cases recruited from child psychiatric clinics of Peking University Institute of Mental Health. Nine hundred fifty seven non-mentally ill control subjects were ascertained from local elementary schools, healthy blood donors from the Blood Center of the First Hospital, Peking University, and from healthy volunteers at our Institute.
Diagnosis Description	A semi-structured interview was conducted by psychiatrists with the parents and their offspring together using the Clinical Diagnostic Interview Scale (CDIS). The CDIS assesses the three DSM-IV subtypes of ADHD: ADHD inattentive type (ADHD-I), ADHD hyperactive-impulsive type (ADHD-HI), and ADHD combined type (ADHD-C). Teachers were administered the ADHD Rating Scale-IV (ADHD RS-IV), which scored the 18 DSM-IV symptoms of ADHD for frequency of occurrence.
Technique	All of the five SNPs were genotyped using a Taqman allelic genotyping assay on an ABI 7900 HT instrument.
Analysis Method	For the case¨Ccontrol study, we performed a logistic regression of case status on genotype with gender and age as covariates due to the significant difference of gender composition and age between cases and controls while only age was a covariate in the genderspecific analyses. These analyses were performed in SPSS version 17.0 and the accepted level of significance was 0.05 for all analyses. All tests were two-tailed.
Result Description	The association with MAOA was restricted to males, especially males with ADHD-HI. Logistic regression analyses of data from 1,824 cases and 957 controls did not indicate any association. We used analysis of covariance to analyze the association between MAOA genotype with the "inhibit" factor of the Behavior Rating Inventory of Executive Function (BRIEF) in 640 probands and performance on the Stroop test in 810 probands. Probands homozygous for risk alleles found in the TDT test had higher "inhibit" scores on the BRIEF scale which represents more severe impulsivity; this results also was restricted to males. No association was found with Stroop test performance. In conclusion, our results provide some evidence that MAOA may be associated with the ADHD-HI subtype and support the association between MAOA and impulsivity, which may be a potential endophenotype of ADHD. However, the results were strongly influenced by gender.

SNPs reported by this study (count: 5)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs3027400		T	TDT P-value=0.615 in all ADHD, P-value=0.212 in male ADHD, P-value=0.136 in female ADHD; P-value=0.951 in all ADHD-I, P-value=0.327 in male ADHD-I, P-value=0.085 in female ADHD-I; P-value=0.808 in all ADHD-C, P-value=0.948 in male ADHD-C, P-value=0.631 in female ADHD-C; Nominal P-value=0.011, Empirical P-value=0.031, X²=6.429 in ADHD-HI Trios; Nominal P-value=0.011, Empirical P-value=0.016, X²=6.533; Logistic Regression, P-value=0.777, OR=1.015; P-value<0.001, OR=0.982 after controlling for potentially confounding factors like age; P-value<0.001, OR=0.216 after controlling for potentially confounding factors like gender	No biased transmission of any allele of any of the five eval...... No biased transmission of any allele of any of the five evaluated polymorphisms was observed for the entire sample of ADHD, ADHD-I, or ADHD-C. We only found biased transmission of these SNPs in the ADHD-HI subgroup. No association was found for ADHD females or subtypes. The results showed that there was no different genotype distribution of any SNP after controlling for potentially confounding factors including gender and age. More...	Significant
rs2239448		T	TDT P-value=0.480 in all ADHD, P-value=0.155 in male ADHD, P-value=0.170 in female ADHD; P-value=0.671 in all ADHD-I, P-value=0.216 in male ADHD-I, P-value=0.152 in female ADHD-I; P-value=0.856 in all ADHD-C, P-value=0.948 in male ADHD-C, P-value=0.527 in female ADHD-C; Nominal P-value=0.024, Empirical P-value=0.067, X²=5.121 in ADHD-HI Trios; Nominal P-value=0.023, Empirical P-value=0.039, X²=5.143; Logistic Regression, P-value=0.806, OR=1.013; P-value<0.001, OR=0.982 after controlling for potentially confounding factors like age; P-value<0.001, OR=0.221 after controlling for potentially confounding factors like gender	No biased transmission of any allele of any of the five eval...... No biased transmission of any allele of any of the five evaluated polymorphisms was observed for the entire sample of ADHD, ADHD-I, or ADHD-C. We only found biased transmission of these SNPs in the ADHD-HI subgroup. No association was found for ADHD females or subtypes. The results showed that there was no different genotype distribution of any SNP after controlling for potentially confounding factors including gender and age. More...	Significant
rs3788862		A	TDT P-value=0.172 in all ADHD, P-value=0.023 in male ADHD, P-value=0.144 in female ADHD; P-value=0.479 in all ADHD-I, P-value=0.162 in male ADHD-I, P-value=0.285 in female ADHD-I; P-value=0.562 in all ADHD-C, P-value=0.302 in male ADHD-C, P-value=0.273 in female ADHD-C; Nominal P-value=0.056, Empirical P-value=0.123, X²=3.667 in ADHD-HI Trios; Nominal P-value=0.034, Empirical P-value=0.068, X²=4.481; Logistic Regression, P-value=0.694, OR=0.979; P-value<0.001, OR=0.982 after controlling for potentially confounding factors like age; P-value<0.001, OR=0.219 after controlling for potentially confounding factors like gender	No biased transmission of any allele of any of the five eval...... No biased transmission of any allele of any of the five evaluated polymorphisms was observed for the entire sample of ADHD, ADHD-I, or ADHD-C. We only found biased transmission of these SNPs in the ADHD-HI subgroup. No association was found for ADHD females or subtypes. In male ADHD trios, the A allele of rs3788862 was over-transmitted, and for ADHD subtypes, we also found the same associations in males with ADHD-HI as were seen in the analysis of the entire ADHD-HI sample. The results showed that there was no different genotype distribution of any SNP after controlling for potentially confounding factors including gender and age. More...	Significant
rs5905859		C	TDT P-value=0.532 in all ADHD, P-value=0.215 in male ADHD, P-value=0.235 in female ADHD; P-value=0.761 in all ADHD-I, P-value=0.272 in male ADHD-I, P-value=0.152 in female ADHD-I; P-value=0.761 in all ADHD-C, P-value=0.844 in male ADHD-C, P-value=0.746 in female ADHD-C; Nominal P-value=0.011, Empirical P-value=0.031, X²=6.429 in ADHD-HI Trios; Nominal P-value=0.011, Empirical P-value=0.016, X²=6.533; Logistic Regression, P-value=0.657, OR=1.023; P-value<0.001, OR=0.982 after controlling for potentially confounding factors like age; P-value<0.001, OR=0.224 after controlling for potentially confounding factors like gender	No biased transmission of any allele of any of the five eval...... No biased transmission of any allele of any of the five evaluated polymorphisms was observed for the entire sample of ADHD, ADHD-I, or ADHD-C. We only found biased transmission of these SNPs in the ADHD-HI subgroup. No association was found for ADHD females or subtypes. The results showed that there was no different genotype distribution of any SNP after controlling for potentially confounding factors including gender and age. More...	Significant
rs1137070		T	TDT P-value=0.633 in all ADHD, P-value=0.268 in male ADHD, P-value=0.230 in female ADHD; P-value=0.752 in all ADHD-I, P-value=0.251 in male ADHD-I, P-value=0.145 in female ADHD-I; P-value=0.614 in all ADHD-C, P-value=0.732 in male ADHD-C, P-value=0.631 in female ADHD-C; Nominal P-value=0.008, Empirical P-value=0.019, X²=7 in ADHD-HI Trios; Nominal P-value=0.014, Empirical P-value=0.029, X²=6; Logistic Regression, P-value=0.782, OR=0.985; P-value<0.001, OR=0.983 after controlling for potentially confounding factors like age; P-value<0.001, OR=0.221 after controlling for potentially confounding factors like gender	No biased transmission of any allele of any of the five eval...... No biased transmission of any allele of any of the five evaluated polymorphisms was observed for the entire sample of ADHD, ADHD-I, or ADHD-C. We only found biased transmission of these SNPs in the ADHD-HI subgroup. No association was found for ADHD females or subtypes. The results showed that there was no different genotype distribution of any SNP after controlling for potentially confounding factors including gender and age. More...	Significant

Genes reported by this study (count: 1)