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

Detail ...

Study Report

Basic Info

Reference	Wigg KG, 200819076634
Citation	Wigg K. G., Feng Y., Crosbie J., Tannock R., Kennedy J. L., Ickowicz A., Malone M., Schachar R. and Barr C. L. (2008) "Association of ADHD and the Protogenin gene in the chromosome 15q21.3 reading disabilities linkage region." Genes Brain Behav, 7(8): 877-86.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	253 nuclear families
Predominant Ethnicity	Caucasian
Population	Canada
Gender	242 boys and 58 girls
Age Group	Children/Adolescents : 7-16 years

Detail Info

Summary	To continue study of 15q, they tested a coding region change in DYX1C1, followed bymarkers across the gene Protogenin (PRTG) in 253 ADHD nuclear families. PRTG was chosen based on its location and because it is closely related to DCC and Neogenin, two genes known to guidemigratory cells and axons during development. The markers in DYX1C1 were not associated to ADHD when analyzed individually; however, six markers in PRTG showed significant association with ADHD as a categorical trait. Haplotypes in both genes showed evidence for association. They identified association with ADHD symptoms measured as quantitative traits in PRTG, but no evidence for association with two key components of reading, word identification and decoding was observed.
Total Sample	The study sample was comprised of 253 nuclear families from the Toronto area, including 47 affected siblings. This gave a total of 300 affected children (242 boys and 58 girls). The majority of the families reported their ethnic background to be of European Caucasian descent, while 10% of families were of other or mixed background, including Chinese, African, Indian and native Canadians.
Sample Collection	European Caucasian descent, and other or mixed background, including Chinese, African, Indian and native Canadians
Diagnosis Description	Probands and affected siblings were recruited from the Child Development and Neuropsychiatry Clinics at the Hospital for Sick Children. The selection criteria for inclusion were subjects between the ages of 7 and 16 years that met the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition (DSM-IV) criteria for ADHD. For the diagnoses of ADHD and information on ADHD symptoms, two informants were used: the parents completed the Parent Interview for Child Symptoms and the teachers were administered the Teacher Telephone Interview for Children's Academic Performance. For the affected children, the distribution among the DSM-IV ADHD subtypes was 14% of the predominantly hyperactive/impulsive subtype, 24% of the predominantly inattentive subtype and 62% of the combined subtype.
Technique	DNA was extracted from blood lymphocytes using a high salt extraction method. The SNPs across the PRTG gene were selected using the Tagger Pairwise Method as implemented on the International HapMap Project Browser as well as three publicly reported synonymous and nonsynonymous SNPs. For DYX1C1, eight SNPs were genotyped, eight of these had been previously genotyped in 186 of the ADHD families and the genotyping was updated in our expanded sample. Two additional SNPs, rs600753 and rs16787 in the DYX1C1 gene were also genotyped. The SNP assays weremanufactured by Applied Biosystems as either Assays-On-Demand or as Assays-by-Design.
Analysis Method	The extended transmission disequilibrium test program was used to test for the biased transmission of alleles at each marker, based on the categorical diagnosis of DSM-IV ADHD. Permutation analysis for the categorical results was performed using the UNPHASED 3.0 program. The transmission of the haplotypes was analyzed with the TRANSMIT program.
Result Description	The markers in DYX1C1 were not associated to ADHD when analyzed individually; however, six markers in PRTG showed significant association with ADHD as a categorical trait. Haplotypes in both genes showed evidence for association. They identified association with ADHD symptoms measured as quantitative traits in PRTG, but no evidence for association with two key components of reading, word identification and decoding was observed.

SNPs reported by this study (count: 26)

SNP	Allele Change	Statistical Values	Author Comments	Result of Statistical Analysis
rs9920546	A/G	TDT P-value=0.47, X²=0.521	no evidence for association no evidence for association	Non-significant
rs1011061	T/C	TDT P-value=0.842, X²=0.04	no evidence for association no evidence for association	Non-significant
rs11071200	T/G	TDT P-value=0.026, X²=4.959	was significantly associated to ADHD was significantly associated to ADHD	Significant
rs11629841	A/C	TDT P-value=0.488, X²=0.482	no evidence for association no evidence for association	Non-significant
rs11852746	A/G	TDT P-value=0.729, X²=0.12	no evidence for association no evidence for association	Non-significant
rs11854213	T/C	TDT P-value=0.773, X²=0.083	no evidence for association no evidence for association	Non-significant
rs12438177	C/T	TDT P-value=0.775, X²=0.082	no evidence for association no evidence for association	Non-significant
rs12591646	A/C	TDT P-value=0.025, X²=5.026	was significantly associated to ADHD was significantly associated to ADHD	Significant
rs1438914	T/A	TDT P-value=0.016, X²=5.76	was significantly associated to ADHD was significantly associated to ADHD	Significant
rs1550326	C/A	TDT P-value=0.209, X²=1.576	no evidence for association no evidence for association	Non-significant
rs2007494	T/A	TDT P-value=0.114, X²=2.5	no evidence for association no evidence for association	Non-significant
rs16976466	G/A	TDT P-value=0.584, X²=0.3	no evidence for association no evidence for association	Non-significant
rs3743204	C/A	TDT P-value=0.151, X²=2.063	no evidence for association no evidence for association	Non-significant
rs2414424	A/G	TDT P-value=0.005, X²=8.067; P-value=0.046 after permutation testing	was significantly associated to ADHD was significantly associated to ADHD	Significant
rs3985768	T/A	TDT P-value=0.832, X²=0.045	no evidence for association no evidence for association	Non-significant
rs3743205	G/A	TDT P-value=0.574, X²=0.316	no evidence for association no evidence for association	Non-significant
rs492363	T/C	TDT P-value=0.459, X²=0.549	no evidence for association no evidence for association	Non-significant
rs4774800	A/G	TDT P-value=0.18, X²=1.795	no evidence for association no evidence for association	Non-significant
rs558290	A/G	TDT P-value=0.142, X²=2.16	no evidence for association no evidence for association	Non-significant
rs530798	T/C	TDT P-value=0.375, X²=0.786	no evidence for association no evidence for association	Non-significant
rs692691	G/A	TDT P-value=0.754, X²=0.098	no evidence for association no evidence for association	Non-significant
rs600753	G/A	TDT P-value=0.492, X²=0.472	no evidence for association no evidence for association	Non-significant
rs7165971	A/G	TDT P-value=0.011, X²=6.416	was significantly associated to ADHD was significantly associated to ADHD	Significant
rs7162879	T/A	TDT P-value=0.018, X²=5.555	was significantly associated to ADHD was significantly associated to ADHD	Significant
rs934886	C/T	TDT P-value=0.455, X²=0.558	no evidence for association no evidence for association	Non-significant
rs7183943	T/C	TDT P-value=0.581, X²=0.305	no evidence for association no evidence for association	Non-significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DYX1C1 1249G/T	G/T		TDT P-value=1.00, X²=0.00 TDT P-value=1.00, X²=0.00	no evidence for association	Non-significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
DYX1C1	haplotypes of the six markers P-value=0.078, X²=6...... haplotypes of the six markers P-value=0.078, X²=6.809, df=1, no significant association More...	Non-significant
PRTG	haplotype AA P-value=0.007, X² (df=1)=7.155; hapl...... haplotype AA P-value=0.007, X² (df=1)=7.155; haplotype GC P-value=0.023, X² (df=1)=5.208; P-value=0.033, X² (df=3)=8.7482 in global chi-square test; P-value=0.026, chi-squared test on 2 df for haplotypes with frequency >10%=7.2969 of rs7165971 and rs12591646; haplotype AAC P-value=0.017, X² (df=1)=5.670; P-value=0.018, X² (df=6) =15.258 in global chi-square test; P-value=0.007, chi-squared test on 3 df for haplotypes with frequency >10%=12.051 of rs2414424, rs3985768 and rs1011061; showed significant association with ADHD More...	Significant