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	Todd RD, 200312556914
Citation	Todd R. D., Lobos E. A., Sun L. W. and Neuman R. J. (2003) "Mutational analysis of the nicotinic acetylcholine receptor alpha 4 subunit gene in attention deficit/hyperactivity disorder: evidence for association of an intronic polymorphism with attention problems." Mol Psychiatry, 8(1): 103-8.
Study Design	family-based
Study Type	Candidate-gene association study and Mutational study
Sample Size	178 families
Predominant Ethnicity	Caucasian
Population	USA
Gender	54.4% male
Age Group	Children/Adolescents : 7-17 years

Detail Info

Summary	In this study, individuals with two independent familial subtypes of ADHD defined by latent class analysis were systematically screened for sequence variations in the coding regions and intron/exon junctions of the nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4). Common polymorphisms were used for transmission disequilibrium test (TDT) analyses. A significant association was found for a 5' intron 2 single nucleotide polymorphism and severe inattention problems. The location of the polymorphism is compatible with it affecting pre-mRNA stability or splicing.
Total Sample	The samples used here represent the first 178 interviewed families in which one twin had a diagnosis of interest and DNA was available for all family members. The DHPLC screening sample consisted of 85 individuals in the severe attention problems latent class and 87 individuals in the severe combined problems latent class. The sample for TDT analysis consisted of 94 trios assigned to the severe inattention problems latent class and 101 trios in which the offspring was assigned to the severe combined latent class (one affected offspring plus both biological parents).
Sample Collection	The participants of this study are individuals identified in a birth records-based twin study from the state of Missouri.
Diagnosis Description	One parent and both twins were independently interviewed by different interviewers using a DSM-IV version of the Diagnostic Interview for Children and Adolescent (DICA-R) called the MAGIC. Of these trios, 62 contained an offspring with DSM-IV combined subtype ADHD and 87 contained an offspring with DSM-IV primarily inattentive subtype ADHD.
Technique	Primers were chosen to flank protein coding exons including 20-50 base pairs of surrounding intronic sequence as judged by DNA sequence information from GenBank (access numbers NT_011333.4, X87629, X89721-6, L35901, U62433 and Y08421). PCR product amplification, DHPLC analysis and confirmation of genomic DNA sequence variation by DNA sequencing have been previously described.
Analysis Method	All analyses were completed using the ETDT software. For polymorphic markers with more than two alleles, a logistic model performs a global allelewise analysis to test preferential transmission of alleles across all heterozygous parental genotypes. The ETDT also performs the traditional transmission distortion test for each allele.
Result Description	A significant association was found for a 5' intron 2 single nucleotide polymorphism and severe inattention problems (P=0.007, effect size=4, 95% CI 1.3-14.1). The location of the polymorphism is compatible with it affecting pre-mRNA stability or splicing.

Other variant reported by this study (count: 3)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
CHRNA4 exon2 211A/G	A/G		allelic TDT P-value=0.052, corrected P-value=0.1 in DSM-IV A...... allelic TDT P-value=0.052, corrected P-value=0.1 in DSM-IV ADHD; allelic TDT P-value=0.394, corrected P-value=0.632 in DSM-IV combined; allelic TDT P-value=0.046, corrected P-value=0.089 in DSM-IV inattentive; allelic TDT P-value=0.144, corrected P-value=0.267 in latent-class combined; allelic TDT P-value=0.251, corrected P-value=0.44 in latent-class inattentive More...	no significant association with DSM-IV or latent-class-defined ADHD after correcting for multiple comparisons	Significant
CHRNA4 exon2 215A/G	A/G		allelic TDT P-value=0.028, corrected P-value=0.055 in DSM-IV...... allelic TDT P-value=0.028, corrected P-value=0.055 in DSM-IV ADHD; allelic TDT P-value=0.18, corrected P-value=0.327 in DSM-IV combined; allelic TDT P-value=0.039, corrected P-value=0.076 in DSM-IV inattentive; allelic TDT P-value=1, corrected P-value=1 in latent-class combined; allelic TDT P-value=0.007, corrected P-value=0.015 in latent-class inattentive More...	significant association with latent-class-defined inattentive ADHD after correcting for multiple comparisons	Significant
CHRNA4 exon2 150C/T	C/T		allelic TDT P-value=0.052, corrected P-value=0.1 in DSM-IV A...... allelic TDT P-value=0.052, corrected P-value=0.1 in DSM-IV ADHD; allelic TDT P-value=0.394, corrected P-value=0.632 in DSM-IV combined; allelic TDT P-value=0.046, corrected P-value=0.089 in DSM-IV inattentive; allelic TDT P-value=0.144, corrected P-value=0.267 in latent-class combined; allelic TDT P-value=0.251, corrected P-value=0.44 in latent-class inattentive More...	no significant association with DSM-IV or latent-class-defined ADHD after correcting for multiple comparisons	Significant

Genes reported by this study (count: 1)