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	Shang CY, 201120800641
Citation	Shang C. Y., Gau S. S., Liu C. M. and Hwu H. G. (2011) "Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan." Prog Neuropsychopharmacol Biol Psychiatry, 35(2): 421-8.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	273 DSM-IV diagnosed ADHD probands and their family members (n=906)
Predominant Ethnicity	Mongoloid
Population	China
Gender	male: 85.7%
Age Group	Children/Adolescents : mean age was 10.8 (SD=2.5) years

Detail Info

Summary	This Chinese family-based association sample consisted of 273 DSM-IV diagnosed ADHD probands and their family members (n=906). They screened 15 polymorphisms across the DAT1 gene, including 14 single nucleotide polymorphism (SNP) markers and the variable number of tandem repeat (VNTR) polymorphism in 3'-untranslated region (3'UTR). Calculations of pairwise LD revealed three main haplotype blocks (HBs): HB1 (intron 2 through intron 6), HB2 (intron 8 through intron 11), and HB3 (3'UTR). Family-Based Association Tests showed that no allele was significantly more transmitted than expected to the ADHD children for these 15 markers. Haplotype-Based Association Tests showed that a haplotype rs27048 (C)/rs429699 (T) was significantly associated with the inattentive subtype. In quantitative analyses, this haplotype also demonstrated significant association with the inattention severity. Their finding of the haplotype rs27048 (C)/rs429699 (T) as a novel genetic marker in the inattentive ADHD subtype suggests that variation in the DAT1 gene may primarily affect the inattentive subtype of ADHD.
Total Sample	The probands were 273 Chinese children with ADHD, who were recruited consecutively from the Children's Mental Health Center, National Taiwan University Hospital, Taiwan. Families of probands were also recruited, resulting in 906 subjects in total. There were 108 families with one proband, one sibling, and two parents; 9 families with one proband, two siblings, and two parents; 110 trios (one proband plus two parents); 7 families with one proband, one sibling, and one parent; and 39 duos (one proband plus one parent).
Sample Collection	Chinese
Diagnosis Description	The inclusion criteria for the probands were having (1) a clinical diagnosis of ADHD according to the DSM-IV criteria after at least three-visit clinical assessment by board-certificated child psychiatrists with the confirmation by psychiatric interview using the Chinese version of the Kiddie Epidemiologic version of the Schedule for Affective Disorders and Schizophrenia (K-SADS-E); (2) ages ranging from 7 to 18 at assessment; (3) subjects had at least one biological parent; (4) fullscale IQ N80; and (5) both parents of Chinese Han descent. The probands were excluded if they had a history of the following condition as defined by the DSM-IV criteria: schizophrenia, schizoaffective disorder, bipolar disorders, major depression, organic psychosis, or pervasive developmental disorder. A semi-structured interview was conducted by well-trained research assistants with the parents and probands using the Chinese K-SADS-E, which has been widely used in a variety of studies on the mental illness of children and adolescents in Taiwan (Gau and Soong, 1999; Gau et al., 2005).
Technique	Tag SNPs were selected by searching Han Chinese data from the HapMap project (www.hapmap.org) using the Tagger program (de Bakker et al., 2005). All SNP genotypings were performed by the method of matrixassisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Primers and probes flanking the SNPs were designed using SpectroDESIGNER software (Sequenom, San Diego, CA, USA). A DNA fragment (100-300 bp) encompassing the SNP site was amplified using polymerase chain reaction (PCR) (GeneAmp 9700 thermocycler, Applied Biosystems, Branchburg, NJ, USA) according to the manufacturer's instructions.
Analysis Method	The transmission disequilibrium test (TDT) was used to test for transmission of specific alleles from heterozygous parents to affected offsprings. They used the Family-Based Association Test (FBAT) software version 2.0.2 (Laird et al., 2000) to conduct data analysis. In order to minimize the false positive rate, the Bonferroni correction procedure was used to adjust for multiple SNP comparisons in a candidate gene analysis. Haplotype analyses were performed using the Haplotype-Based Association Test (HBAT) in the FBAT program.
Result Description	The major findings of this study were three haplotype blocks (intron 2 through intron 6, intron 8 through intron 11, and 3'UTR), and the haplotype rs27048 (C)/rs429699 (T) was significantly associated with the inattentive subtype. In quantitative analyses, this haplotype also demonstrated significant association with the inattention severity. Their finding of the haplotype rs27048 (C)/rs429699 (T) as a novel genetic marker in the inattentive ADHD subtype suggests that variation in the DAT1 gene may primarily affect the inattentive subtype of ADHD.

SNPs reported by this study (count: 14)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs37022	A/T		T allele FBAT P-value=0.951, Z=0.061 for total sample; A allele FBAT P-value=0.863, Z=0.173 for combined subtype; T allele FBAT P-value=0.819, Z=0.229 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs393795	A/C		C allele FBAT P-value=0.804, Z=0.248 for total sample; A allele FBAT P-value=0.796, Z=0.258 for combined subtype; C allele FBAT P-value=0.574, Z=0.563 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs2937639	A/G		G allele FBAT P-value=0.249, Z=1.154 for total sample; G allele FBAT P-value=0.118, Z=1.565 for combined subtype; G allele FBAT P-value=0.662, Z=0.438 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs37020	G/T		G allele FBAT P-value=0.271, Z=1.1 for total sample; G allele FBAT P-value=0.038, Z=2.073 for combined subtype; T allele FBAT P-value=0.816, Z=0.232 for inattentive subtype	no significant associations in the total sample; showed bias...... no significant associations in the total sample; showed biased transmission for ADHD children in combined subtype More...	Significant
rs403636	G/T		G allele FBAT P-value=0.362, Z=0.911 for total sample; G allele FBAT P-value=0.109, Z=1.604 for combined subtype; T allele FBAT P-value=0.816, Z=0.232 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs429699	C/T		T allele FBAT P-value=0.068, Z=1.824 for total sample; T allele FBAT P-value=0.269, Z=1.105 for combined subtype; T allele FBAT P-value=0.017, Z=2.393 for inattentive subtype	displayed trends for association with ADHD; showed biased tr...... displayed trends for association with ADHD; showed biased transmission for ADHD children in inattentive subtype More...	Significant
rs40184	G/A		G allele FBAT P-value=0.639, Z=0.469 for total sample; A allele FBAT P-value=0.357, Z=0.921 for combined subtype; G allele FBAT P-value=0.081, Z=1.746 for inattentive subtype	no significant associations in the total sample; displayed a...... no significant associations in the total sample; displayed a trend for association in inattentive subtype More...	Non-significant
rs40358	T/G		T allele FBAT P-value=0.157, Z=1.414 for total sample; T allele FBAT P-value=0.054, Z=1.93 for combined subtype; T allele FBAT P-value=0.637, Z=0.471 for inattentive subtype	no significant associations in the total sample; displayed a...... no significant associations in the total sample; displayed a trend for association in combined subtype More...	Non-significant
rs27048	C/T		C allele FBAT P-value=0.695, Z=0.392 for total sample; T allele FBAT P-value=0.552, Z=0.594 for combined subtype; C allele FBAT P-value=0.131, Z=1.511 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs27072	C/T		T allele FBAT P-value=0.586, Z=0.544 for total sample; T allele FBAT P-value=0.227, Z=1.209 for combined subtype; C allele FBAT P-value=0.718, Z=0.361 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs1042098	T/C		T allele FBAT P-value=0.131, Z=1.51 for total sample; T allele FBAT P-value=0.267, Z=1.109 for combined subtype; T allele FBAT P-value=0.577, Z=0.557 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs2617605	A/G		G allele FBAT P-value=0.306, Z=1.025 for total sample; G allele FBAT P-value=0.227, Z=1.207 for combined subtype; G allele FBAT P-value=0.701, Z=0.384 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs466630	G/C		C allele FBAT P-value=0.832, Z=0.213 for total sample; C allele FBAT P-value=0.705, Z=0.378 for combined subtype; C allele FBAT P-value=0.497, Z=0.679 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant
rs463379	G/C		G allele FBAT P-value=1, Z=0 for total sample; G allele FBAT P-value=0.604, Z=0.518 for combined subtype; C allele FBAT P-value=0.574, Z=0.563 for inattentive subtype	no significant associations in the total sample no significant associations in the total sample	Non-significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 3'-UTR VNTR	9/10 repeats		10-repeat allele FBAT P-value=0.059, Z=1.886 for total sampl...... 10-repeat allele FBAT P-value=0.059, Z=1.886 for total sample; 10-repeat allele FBAT P-value=0.423, Z=0.801 for combined subtype; 10-repeat allele FBAT P-value=0.061, Z=1.877 for inattentive subtype More...	displayed trends for association with ADHD; displayed a trend for association in inattentive subtype	Non-significant

Genes reported by this study (count: 1)