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	Hawi Z, 200516380908
Citation	Hawi Z., Segurado R., Conroy J., Sheehan K., Lowe N., Kirley A., Shields D., Fitzgerald M., Gallagher L. and Gill M. (2005) "Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder." Am J Hum Genet, 77(6): 958-65.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	179 nuclear families
Predominant Ethnicity	Irish
Population	Ireland
Age Group	Children/Adolescents

Detail Info

Summary	They have examined monoaminergic candidate genes for possible genetic association with ADHD in the Irish population, focusing particularly on genes of the dopaminergic and serotonergic systems. They have observed that several of these genes are associated with ADHD, including DAT1, DBH, DRD4, DRD5, and 5HT1B. Here, they present what appears to be a systematic overtransmission of paternal alleles at candidate genes associated with ADHD. For the nine genes included in the analysis, the overall odds ratio for paternal transmission was 2, compared with 1.3 for maternal transmission (paternal vs. maternal X²=9.6; P=0.0019). Transmission to females, from either parent, was significantly stronger than to males.
Total Sample	A total of 179 Irish ADHD-affected nuclear families were included in the current study.
Sample Collection	A total of 179 Irish ADHD-affected nuclear families were included in the current study.
Diagnosis Description	The sample was ascertained and the diagnosis confirmed as described elsewhere (Kirley et al. 2004). In brief, consensus diagnoses were made in accordance with DSM-IV criteria. One or both parents of each child were interviewed using the Child and Adolescent Psychiatric Assessment. To fulfill DSM-IV criteria for symptom pervasiveness, information about ADHD symptoms at school was obtained from teachers through use of the Teacher Telephone Interview, which involved asking teachers about DSM-IV symptoms of ADHD and impairment shown in class. Of the sample, 77% were affected with ADHD-combined type, whereas 15% met research criteria for ADHD-inattentive type, and 8% for ADHD- hyperactive-impulsive type.
Technique	PCR-based genotyping of markers included in this study was conducted using the primer sequences and amplification conditions as described and referenced in table 2 in the original publication.
Analysis Method	The transmission/disequilibrium test (TDT) is a linkage and family-based association test (Spielman et al. 1993) designed to avoid errors in case-control studies that are due to population stratification. It compares the frequency of transmitted and nontransmitted alleles from parents heterozygous for a given polymorphism.
Result Description	For the nine genes included in the analysis, the overall odds ratio for paternal transmission was 2, compared with 1.3 for maternal transmission (paternal vs. maternal x²=9.6, P=0.0019). Transmission to females, from either parent, was significantly stronger than to males. Possible reasons for this preferential transmission include imprinting and ascertainment bias, although results of further analyses show that the latter is unlikely.

SNPs reported by this study (count: 4)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs6296			TDT P-value=0.11, X²=2.9, OR=1.6 for paternel transmission; TDT P-value=0.46, X²=0.73, OR=1.3 for maternal transmission	a trend was seen for paternal transmission and no significan...... a trend was seen for paternal transmission and no significant association was observed for maternal transmission More...	Non-significant
rs3746544			TDT P-value=0.18, X²=2.2, OR=1.5 for paternel transmission; TDT P-value=0.6, X²=0.4, OR=0.8 for maternal transmission	a trend was seen for paternal transmission and no significan...... a trend was seen for paternal transmission and no significant association was observed for maternal transmission More...	Non-significant
rs1843809			TDT P-value=0.001, X²=10.9, OR=3.7 for paternel transmission; TDT P-value=0.09, X²=3.5, OR=1.9 for maternal transmission	nominal significant overtransmission of paternal alleles was...... nominal significant overtransmission of paternal alleles was seen, no significant association was observed for maternal transmission More...	Significant
rs12720373			TDT P-value=0.043, X²=4.6, OR=1.7 for paternel transmission; TDT P-value=0.09, X²=3.3, OR=1.7 for maternal transmission	nominal significant overtransmission of paternal alleles was...... nominal significant overtransmission of paternal alleles was seen, no significant association was observed for maternal transmission More...	Significant

Other variant reported by this study (count: 5)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DDC exon1 ins/del 4bp			TDT P-value=0.18, X²=2.8, OR=3.5 for paternel tra...... TDT P-value=0.18, X²=2.8, OR=3.5 for paternel transmission; TDT P-value=0.63, X²=0.53, OR=1.4 for maternal transmission More...	a trend was seen for paternal transmission and no significant association was observed for maternal transmission	Non-significant
DRD5 5'-flanking (CT/GT/GA)n			TDT P-value=0.0034, X²=9.1, OR=2 for paternel tra...... TDT P-value=0.0034, X²=9.1, OR=2 for paternel transmission; TDT P-value=0.07, X²=3.6, OR=1.5 for maternal transmission More...	nominal significant overtransmission of paternal alleles was seen, no significant association was observed for maternal transmission	Significant
SLC6A4 D17S1294			TDT P-value=0.002, X²=9.9, OR=7.5 for paternel tr...... TDT P-value=0.002, X²=9.9, OR=7.5 for paternel transmission; TDT P-value=1, X²=0.05, OR=0.9 for maternal transmission More...	nominal significant overtransmission of paternal alleles was seen, no significant association was observed for maternal transmission	Significant
SLC6A3 3'-UTR VNTR			TDT P-value=0.048, X²=4.4, OR=1.8 for paternel tr...... TDT P-value=0.048, X²=4.4, OR=1.8 for paternel transmission; TDT P-value=0.41, X²=0.9, OR=0.8 for maternal transmission More...	nominal significant overtransmission of paternal alleles was seen, no significant association was observed for maternal transmission	Significant
TH intron1 (TCAT)n			TDT P-value=0.16, X²=2.5, OR=1.8 for paternel tra...... TDT P-value=0.16, X²=2.5, OR=1.8 for paternel transmission; TDT P-value=0.24, X²=1.7, OR=1.5 for maternal transmission More...	a trend was seen for paternal transmission and no significant association was observed for maternal transmission	Non-significant

Genes reported by this study (count: 9)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DRD5	one marker showed significant overtransmission of paternal a...... one marker showed significant overtransmission of paternal alleles; paternal versus maternal transmissions, combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0024, X²=9.2 when DRD5 was removed in sensitivity analysis More...	Significant
DDC	paternal versus maternal transmissions, 9 genes combined TDT...... paternal versus maternal transmissions, 9 genes combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0026, X²=9 when DDC was removed in sensitivity analysis More...	Non-significant
TPH2	one marker showed significant overtransmission of paternal a...... one marker showed significant overtransmission of paternal alleles; paternal versus maternal transmissions, combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0038, X²=8.3 when TPH2 was removed in sensitivity analysis More...	Significant
SLC6A3	one marker showed significant overtransmission of paternal a...... one marker showed significant overtransmission of paternal alleles; paternal versus maternal transmissions, combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.013, X²=6.1 when SLC6A3 was removed in sensitivity analysis More...	Significant
DRD4	one marker showed significant overtransmission of paternal a...... one marker showed significant overtransmission of paternal alleles; paternal versus maternal transmissions, combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0011, X²=10.6 when DRD4 was removed in sensitivity analysis More...	Significant
TH	paternal versus maternal transmissions, 9 genes combined TDT...... paternal versus maternal transmissions, 9 genes combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0016, X²=9.9 when TH was removed in sensitivity analysis More...	Non-significant
SNAP25	paternal versus maternal transmissions, 9 genes combined TDT...... paternal versus maternal transmissions, 9 genes combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.007, X²=7.3 when SNAP-25 was removed in sensitivity analysis More...	Non-significant
SLC6A4	one marker showed significant overtransmission of paternal a...... one marker showed significant overtransmission of paternal alleles; paternal versus maternal transmissions, combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0085, X²=6.9 when SERT was removed in sensitivity analysis More...	Significant
HTR1B	paternal versus maternal transmissions, 9 genes combined TDT...... paternal versus maternal transmissions, 9 genes combined TDT P-value=0.0019, X²=9.6 (1df), OR=1.56; TDT P-value=0.0017, X²=9.8 when 5HT1B was removed in sensitivity analysis More...	Non-significant