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	Lanktree M, 200818286632
Citation	Lanktree M., Squassina A., Krinsky M., Strauss J., Jain U., Macciardi F., Kennedy J. L. and Muglia P. (2008) "Association study of brain-derived neurotrophic factor (BDNF) and LIN-7 homolog (LIN-7) genes with adult attention-deficit/hyperactivity disorder." Am J Med Genet B Neuropsychiatr Genet, 147B(6): 945-51.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	64 complete trios, 121 cases with a corresponding number of controls
Predominant Ethnicity	Caucasian
Population	Canada
Age Group	Adults : mean age 34.7,SD=12.7

Detail Info

Summary	They tested for association between five BDNF polymorphisms, two LIN-7 polymorphisms and adult ADHD. The sample consisted of 80 trios comprised of an adult ADHD proband and their biological parents and an independent sample of 121 adult ADHD cases and a corresponding number of sex, age, and ethnically matched controls (total 201 probands). Allelic and haplotype association was found between both BDNF and adult ADHD, and LIN-7 and adult ADHD. HapMap indicates BDNF and LIN-7 occur in different haplotype blocks, though some linkage disequilibrium exists between the SNPs in these adjacent genes.
Total Sample	The family sample contains 268 individuals in 64 complete trios (one proband plus two parents), 14 families with one affected and one unaffected child, 4 families with two affected children, and 1 family with one affected and two unaffected children. A case-control sample comprised of 121 cases with a corresponding number of controls matched for age, ethnicity and sex were included. A total of 201 (80+121) probands were included in this study.
Sample Collection	mixed European Caucasian ancestry (94%), African descent and Chinese descent (6%)
Diagnosis Description	The diagnosis of ADHD was based upon fulfilling the criteria for ADHD in the DSM-IV both at the time of interview and during childhood, as recalled by the patient and at least one first-degree relative. In order to rule out additional psychiatric conditions, patients were assessed using the Structural Clinical Interview for DSM-IV (axis I) by a psychiatrist (U.J.).
Technique	Determination of genotypes was performed independently by two lab technicians and in the case of unclear genotypes, the Sequence Detection System ABI 7000 (Applied Biosystem, Foster City, CA) was used. The SNPs were amplified and genotyped using ABI TaqMan 5'-exonuclease Assays-on- DemandTM according to the manufacturer's protocols.
Analysis Method	Chi-square analysis was used to compare allele counts in the case-control sample and transmission disequilibrium test (TDT) in the family sample. Chi-squares were then calculated to compare cases and controls/inferred controls in the combined sample. To examine the LD between polymorphisms the Lewontin D' was calculated, and haplotype frequencies were predicted using the expectation maximization (EM) algorithm as implemented in Haploview.
Result Description	Allelic and haplotype association was found between both BDNF and adult ADHD, and LIN-7 and adult ADHD. HapMap indicates BDNF and LIN-7 occur in different haplotype blocks, though some linkage disequilibrium exists between the SNPs in these adjacent genes.

SNPs reported by this study (count: 7)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs6265	A(M):G(V)		X²=4.41, P-value=0.036 in the family-based sample; X²=2.31, P-value=0.13, OR=1.47 in the case-control sample; X²=6.71, P-value=0.0096, OR=1.65 in the combined samples	showed marginal significance in the family-based sample, and...... showed marginal significance in the family-based sample, and showed association in the combined samples More...	Significant
rs4923463	G:A		X²=3.31, P-value=0.069 in the family-based sample; X²=1.96, P-value=0.16, OR=1.43 in the case-control sample; X²=5.32, P-value=0.021, OR=1.56 in the combined samples	showed association in the combined samples showed association in the combined samples	Significant
rs7103411	T:C		X²=4.57, P-value=0.033 in the family-based sample; X²=1.78, P-value=0.18, OR=1.04 in the case-control sample; X²=5.54, P-value=0.019, OR=1.54 in the combined samples	showed marginal significance in the family-based sample, and...... showed marginal significance in the family-based sample, and showed association in the combined samples More...	Significant
rs11030104	G:A		X²=4.79, P-value=0.029 in the family-based sample; X²=2.51, P-value=0.11, OR=1.48 in the case-control sample; X²=6.93, P-value=0.0085, OR=1.66 in the combined samples	showed marginal significance in the family-based sample, and...... showed marginal significance in the family-based sample, and showed association in the combined samples More...	Significant
rs10835188	A:C		X²=6.42, P-value=0.011 in the family-based sample; X²=1.85, P-value=0.17, OR=1.36 in the case-control sample; X²=7.26, P-value=0.0071, OR=1.61 in the combined samples	C allele was significantly over-transmitted to Adult ADHD pr...... C allele was significantly over-transmitted to Adult ADHD probands in the family-based sample, and showed association in the combined samples More...	Significant
rs3763965	A:T		X²=0.67, P-value=0.41 in the family-based sample; X²=0.04, P-value=0.85, OR=1.04 in the case-control sample; X²=0.2, P-value=0.65, OR=1.07 in the combined samples	no significant differences were observed in all samples no significant differences were observed in all samples	Non-significant
rs2049045	G:C		X²=2.27, P-value=0.13 in the family-based sample; X²=2.64, P-value=0.11, OR=1.51 in the case-control sample; X²=6.1, P-value=0.014, OR=1.6 in the combined samples	showed association in the combined samples showed association in the combined samples	Significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
BDNF	haplotype A-G-A-G-T P-value=0.0086, X² =6.90 in t...... haplotype A-G-A-G-T P-value=0.0086, X² =6.90 in the family-based sample, P-value=0.025, X² =5.04, OR=1.47 in the combined samples; haplotype G-A-G-C-C P-value=0.0054, X² =7.75, OR=0.46 in the case-control sample, P-value=0.0013, X² =10.37, OR=0.50 in the combined samples; allelic and haplotype association was found More...	Significant
LIN7C	haplotype C-T P-value=0.025, X²=5.00 in the famil...... haplotype C-T P-value=0.025, X²=5.00 in the family-based sample, P-value=0.0063, X²=7.47, OR=1.58 in the combined samples; haplotype A-T P-value=0.020, X²=5.46, OR=0.67 in the combined samples; allelic and haplotype association was found More...	Significant