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	Quist JF, 200312556913
Citation	Quist J. F., Barr C. L., Schachar R., Roberts W., Malone M., Tannock R., Basile V. S., Beitchman J. and Kennedy J. L. (2003) "The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder." Mol Psychiatry, 8(1): 98-102.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	115 families with 143 children
Predominant Ethnicity	Caucasian
Population	Canada
Gender	112 males and 31 females
Age Group	Children/Adolescents : 7-16 years

Detail Info

Summary	They tested for linkage disequilibrium between the 5-HT1B G861C polymorphism and ADHD in 115 families using the transmission disequilibrium test (TDT). They found evidence for a trend towards excess transmission of the 861G allele that when further analysed for parental allele transmissions exhibited significantly greater paternal transmission of the G allele to the affected child. Although preliminary, results from this study provide additional evidence that serotonin genes may be important risk factors for the development of ADHD.
Total Sample	The genetic study sample was comprised of 115 families, 24 of which contained one affected sibling in addition to the proband and two of which had two affected siblings in addition to the proband. This gave a total sample of 143 children who met DSM-IV criteria for ADHD, 112 males and 31 females.
Sample Collection	Children between the ages of 7 and 16 years were referred to the Hospital for Sick Children in Toronto, Ontario.
Diagnosis Description	Based on semistructure interview, ADHD symptoms were assessed both at home and at school using the parent interview for child symptoms-revised for DSM-IV (PICS-IV) and teacher telephone interview- revised for DSM-IV (TTI-IV). Children were included in the study based on best estimate diagnosis for one of the three DSM-IV ADHD subtypes (inattentive, hyperactive/impulsive, combined) based on the information from the questionnaires, PICS and TTI interviews, and child assessment. In all, 57 of the children met criteria for the ADHD combined type (CT), 19% were hyperactive/impulsive type (HIT), and 24% were the primarily inattentive type (PIT).
Technique	Standard high salt extraction methods were used to isolate DNA from whole blood lymphocytes. Using a modified protocol of Lappalainen et al a 25ul PCR reaction mixture containing 150 ng of genomic DNA, 0.6 uM each of forward 5'-GAA ACA GAC GCC CAA CAG GAC-3' and reverse 5'-CCA GAA ACC GCG AAA GAA GAT-3' primers, 1X PCR buffer (10mM Tris-HCl, 50mM KCl), 1mM MgCl₂, 0.2mM dNTPs, and 1U Taq polymerase was used to amplify a product containing the HTR1B G861C substitution. PCR conditions consisted of an initial 3-min denaturation followed by 30 cycles of a 30s denaturation at 95^o, 30s annealing at 57^o, and a 30s extension at 72^o ending with a final 7-min extension at 72^o. The 548 bp amplified fragment was digested with HincII at 37^o overnight and subsequently electrophoresed on a 2.5% agarose gel at 100V for 1 h. The presence of the HTR1B 861C allele yielded two fragments of 452 and 96 bp while the presence of the HTR1B 861C allele yielded three fragments of 142, 310 and 96 bp.
Analysis Method	Statistical analysis was performed using the extended transmission disequilibrium program (ETDT version 1.8). The TDT was used to assess for nonrandom transmission of alleles from heterozygous parents to affected offspring by comparing the frequency of transmitted alleles to the frequency of nontransmitted alleles. They used an option of the ETDT program to determine maternal vs paternal transmission.
Result Description	They found evidence for a trend towards excess transmission of the 861G allele (X²=2.91, P=0.09) that when further analysed for parental allele transmissions exhibited significantly greater paternal transmission of the G allele (X²=4.80, P=0.03) to the affected child. Although preliminary, results from this study provide additional evidence that serotonin genes may be important risk factors for the development of ADHD.

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
HTR1B G861C	G/C		allelic TDT P-value=0.09, X²=2.91 in entire sampl...... allelic TDT P-value=0.09, X²=2.91 in entire sample; allelic TDT P-value=0.03, X²=4.80 for paternal transmission; allelic TDT P-value=0.49, X²=0.47 for maternal transmission More...	revealed a trend towards preferential transmission of the 861G allele and exhibited significantly greater paternal transmission of the G allele to the affected child	Significant

Genes reported by this study (count: 1)