ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

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	Johansson S, 201020213726
Citation	Johansson S., Halmoy A., Mavroconstanti T., Jacobsen K. K., Landaas E. T., Reif A., Jacob C., Boreatti-Hummer A., Kreiker S., Lesch K. P., Kan C. C., Kooij J. J., Kiemeney L. A., Buitelaar J. K., Franke B., Ribases M., Bosch R., Bayes M., Casas M., Ramos-Quiroga J. A., Cormand B., Knappskog P. and Haavik J. (2010) "Common variants in the TPH1 and TPH2 regions are not associated with persistent ADHD in a combined sample of 1,636 adult cases and 1,923 controls from four European populations." Am J Med Genet B Neuropsychiatr Genet, 153B(5): 1008-15.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	451 ADHD patients and 584 controls
Predominant Ethnicity	Caucasian
Population	Norway, Spain, Germany, the Netherlands
Gender	Norway, 53% male; the Netherlands, 48% male; Germany, 53% male; Spain, 72% male
Age Group	Adults : adults

Detail Info

Summary	The tryptophan hydroxylase 1 and 2 (TPH1 and TPH2) genes encode the rate-limiting enzymes in the serotonin biosynthesis. Genetic variants in both genes have been implicated in several psychiatric disorders. For attention-deficit/hyperactivity disorder (ADHD) in children, the results are conflicting, and little is known about their role in adult ADHD patients. They therefore first genotype-tagged all common variants within both genes in a Norwegian sample of 451 patients with a diagnosis of adult ADHD and 584 controls. Six of the single nucleotide polymorphisms (SNPs) were subsequently genotyped in three additional independent European Caucasian samples of adult ADHD cases and controls from the International Multicenter persistent ADHD Collaboration (IMpACT). None of the SNPs reached formal study-wide significance in the total meta-analysis sample of 1,636 cases and 1,923 controls, despite having a power of >80% to detect a variant conferring an OR=1.25 at P-value=0.001 level. Only the TPH1 SNP rs17794760 showed nominal significance [OR=0.84 (0.71-1.00), P-value=0.05]. In conclusion, in the single largest ADHD genetic study of TPH1 and TPH2 variants presented to date (n=3,559 individuals), they did not find consistent evidence for a substantial effect of common genetic variants on persistent ADHD.
Total Sample	The total sample included 1,636 adult ADHD patients and 1,923 controls' all of Caucasian origin from Norway, Spain, Germany, and the Netherlands recruited into the IMpACT.
Replication Size	1,185 adult cases and 1,339 controls
Sample Collection	Caucasian origin
Diagnosis Description	all patients have been extensively examined by an experienced psychiatrist and diagnosed with ADHD according to the diagnostic criteria of Diagnostic and Statistical Manual for Mental Disorders-IV(DSM-IV), with onset of symptoms before the age of 7 years via retrospective diagnosis (which was confirmed by a family member, wherever possible), lifelong persistence of symptoms, and current diagnosis.
Technique	Genotyping of the Norwegian samples: DNA was extracted either from whole blood, or from saliva using the OrageneTM DNA Self-Collection Kit from DNA Genotek (DNA Genotek Inc., Ontario, Canada). DNA from cases and controls were inter-mixed on 96-well plates with a minimum of two internal controls and two blank samples on each plate. Genotyping was performed using the MassARRAY iPLEX System (SEQUENOM, Inc., San Diego, CA) by CIGENE at the national technology platform, and supported by the Functional Genomics Programme (FUGE) in the Research Council of Norway. Genotyping of the replication samples: samples from Spain and the Netherlands were genotyped together with an additional smaller Norwegian sample in one multiplex reaction using the MassARRAY iPLEX System at CIGENE in Norway. The German samples were genotyped using the same multiplex reaction at Wurtzburg, Germany.
Analysis Method	For single marker analysis of dichotomous traits, they focused on an additive allelic model either with the chi-square test or by using logistic regression with gender as a cofactor as implemented in the PLINK software. For the meta-analysis, they considered only an additive allelelic mode of inheritance and applied a random effect analysis as implemented by the 'metan' command in Stata 8.2 (Stata Statistical Software, Stata Corp., College Station, TX), with the estimate of heterogeneity being taken from the Mantel-Haenszel model. For more detailed information, please refer to the original article.
Result Description	None of the SNPs reached formal study-wide significance in the total meta-analysis sample of 1,636 cases and 1,923 controls, despite having a power of >80% to detect a variant conferring an OR=1.25 at P-value=0.001 level. Only the TPH1 SNP rs17794760 showed nominal significance [OR=0.84 (0.71-1.00), P-value=0.05]. In conclusion, in the single largest ADHD genetic study of TPH1 and TPH2 variants presented to date (n=3,559 individuals), they did not find consistent evidence for a substantial effect of common genetic variants on persistent ADHD.

SNPs reported by this study (count: 27)

SNP	Statistical Values	Author Comments	Result of Statistical Analysis
rs591556	logistic regression P-value=0.74, OR=0.96	no significant association no significant association	Non-significant
rs4760820	logistic regression P-value=0.31, OR=1.1; meta-analysis P-value=0.10, OR=1.10	no significant association no significant association	Non-significant
rs4760818	logistic regression P-value=0.08, OR=1.26; meta-analysis P-value=0.19, OR=0.84	no significant association no significant association	Non-significant
rs4565946	logistic regression P-value=0.79, OR=1.02	no significant association no significant association	Non-significant
rs7963717	logistic regression P-value=0.21, OR=0.8; meta-analysis P-value=0.31, OR=1.10	no significant association no significant association	Non-significant
rs7955501	logistic regression P-value=0.23, OR=1.12	no significant association no significant association	Non-significant
rs7305115	logistic regression P-value=0.24, OR=1.11; meta-analysis P-value=0.9, OR=0.99	no significant association no significant association	Non-significant
rs623580	logistic regression P-value=0.09, OR=0.85	no significant association no significant association	Non-significant
rs12231356	logistic regression P-value=0.93, OR=0.98	no significant association no significant association	Non-significant
rs11615016	logistic regression P-value=0.42, OR=0.88	no significant association no significant association	Non-significant
rs1386496	logistic regression P-value=0.08, OR=1.27, meta-analysis P-value=0.24, OR=0.89	no significant association no significant association	Non-significant
rs1352250	logistic regression P-value=0.33, OR=1.09	no significant association no significant association	Non-significant
rs10879358	logistic regression P-value=0.16, OR=1.14	no significant association no significant association	Non-significant
rs10879357	logistic regression P-value=0.44, OR=1.08	no significant association no significant association	Non-significant
rs11606304	logistic regression P-value=0.77, OR=1.05	no significant association no significant association	Non-significant
rs11178999	logistic regression P-value=0.2, OR=0.87	no significant association no significant association	Non-significant
rs17794760	logistic regression P-value=0.012, OR=0.74; meta-analysis P-value=0.05, OR=0.84	showed nominal association with ADHD in the Norwegian sample...... showed nominal association with ADHD in the Norwegian sample and in the meta-analysis, but this association did not survive correction for multiple testing More...	Significant
rs17722134	logistic regression P-value=0.71, OR=0.91	no significant association no significant association	Non-significant
rs1800532	logistic regression P-value=0.21, OR=1.12	no significant association no significant association	Non-significant
rs1799913	logistic regression P-value=0.39, OR=1.08	no significant association no significant association	Non-significant
rs169806	logistic regression P-value=0.47, OR=1.07	no significant association no significant association	Non-significant
rs1487275	logistic regression P-value=0.85, OR=1.02	no significant association no significant association	Non-significant
rs17110747	logistic regression P-value=0.39, OR=1.12	no significant association no significant association	Non-significant
rs17110690	logistic regression P-value=0.69, OR=1.04	no significant association no significant association	Non-significant
rs10488683	logistic regression P-value=0.48, OR=1.07	no significant association no significant association	Non-significant
rs10832876	logistic regression P-value=0.17, OR=1.15	no significant association no significant association	Non-significant
rs10879354	logistic regression P-value=0.06, OR=1.19	no significant association no significant association	Non-significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
TPH1	nine markers haplotype P-value=0.02, OR=0.74 nine markers haplotype P-value=0.02, OR=0.74	Significant
TPH2	a three-marker haplotype made up by rs7305115, rs4760818, an...... a three-marker haplotype made up by rs7305115, rs4760818, and rs4760820, omnibus P-value=0.02 More...	Significant