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	Lasky-Su J, 200818821565
Citation	Lasky-Su J., Neale B. M., Franke B., Anney R. J., Zhou K., Maller J. B., Vasquez A. A., Chen W., Asherson P., Buitelaar J., Banaschewski T., Ebstein R., Gill M., Miranda A., Mulas F., Oades R. D., Roeyers H., Rothenberger A., Sergeant J., Sonuga-Barke E., Steinhausen H. C., Taylor E., Daly M., Laird N., Lange C. and Faraone S. V. (2008) "Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1345-54.
Study Design	family-based
Study Type	GWAS
Sample Size	958 trios
Predominant Ethnicity	Caucasian
Population	Belgium, Germany, Ireland, the Netherlands, Spain, Switzerland, United Kingdom, Israel
Gender	816(86.99%) males
Age Group	Children/Adolescents : aged 5-17, mean age 10.88 years (SD=2.81)

Detail Info

Summary	In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband-parent trios. After applying data cleaning procedures 429,981 autosomal SNPs in 909 family trios were examined. They generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome-wide association analyses.With the PBAT screening algorithm, they identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. They also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association p-values with a magnitude less than 10-5 ,are discussed in this manuscript. Seventeen of these candidate genes had association p-values lower then 0.01: SLC6A1, SLC9A9,HES1, ADRB2,HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test p-values lower than 0.01 and multiple association p-values at a magnitude of 10-5 in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirmthe proposed genetic variants for ADHD.
Total Sample	A total of 958 affected proband-parent trios were initially selected for the GWAS scan. A total of 2,803 individuals, 1,865 founders and 938 non-founders were included after the cleaning process. Of these individuals, 29 offspring did not have clinical data and/or parental genotypes resulting in 909 individuals used in the analysis.
Sample Collection	Families were collected by the International Multicenter ADHD Genetics (IMAGE) project. Family members were Caucasians of European origin from seven countries around Europe including Belgium, Germany, Ireland, the Netherlands, Spain, Switzerland, and The United Kingdom, as well as Israel.
Diagnosis Description	Of 958 affected proband-parent trios, 936 probands were initially ascertained as having DSM-IV combined type ADHD. Twenty-two probands who did not meet combined subtype ADHD diagnosis were included because they either met the criteria for the inattentive or hyperactive subtypes, or theymissed the DSM-IV combined type diagnosis by a single item. Exclusion criteria were autism, epilepsy, IQ<70, brain disorders and any genetic or medical disorder associated with externalizing behaviors that might mimic ADHD. For detailed information about clinical measures, please refer to the origianl paper.
Technique	Details of the genotyping and data cleaning process were reported elsewhere (Neale et al., 2008). Briefly, genotyping was performed by Perlegen Sciences using the Perlegen platform. The Perlegen Array has 600,000 tagging SNPs designed to be in high linkage disequilibrium with untyped SNPs for the three HapMap populations. Genotype data cleaning and quality control procedures were done by The National Center for Biotechnology Information (NCBI) using the GAIN QA/QC Software Package (version 0.7.4) developed by Goncalo Abecasis and Shyam Gopalakrishnan at the University of Michigan. For more information about quality control metrics, please refer to the original paper.
Analysis Method	They analyzed their data using the FBAT¨CPC methodology in the context of the PBAT screening algorithm. They also performed a cluster analysis in PLINK through a linkage clustering algorithm that is based on pairwise identity-by-state distance, to identify a predominant homogeneous cluster in their sample. Information from this cluster was used to rank-order the SNPs using the PBAT screening algorithm. Using the PBAT screening algorithm they only formally test the top 10 ranked SNPs, and therefore genome-wide significance can be established using a much more liberal threshold than the 10-8 that has been suggested for formal testing of all SNPs. In all analyses, they considered additive, dominant, and recessive genetic models.
Result Description	Two SNPs achieved significance within the specified GWAS analysis. If adjust for selected SNPs from all 18 GWAS analyses, these SNPs do not achieve significance. Among all 18 GWAS analyses, there were 58 association tests with 46 unique SNPs that had a P-value<10-5. There were numerous associations at the candidate gene SNPs with a P-value<0.01.

SNPs reported by this study (count: 49)

SNP	Statistical Values	Author Comments	Result of Statistical Analysis
rs1018040	P-value=4.64E-06 under Additive model for FBAT-PC all symptoms; P-value=2.97E-06 under Dominant model for FBAT-PC all symptoms; P-value=8.20E-06 under Additive model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs10767942	P-value=7.90E-06 under Dominant model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs10895959	P-value=3.00E-06 under Recessive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs10227331	P-value=3.79E-06 under Recessive model for IA symptom count	association finding with P-value association finding with P-value	Trend
rs10421632	P-value=9.68E-06 under Additive model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs17281813	P-value=3.46E-06 under Recessive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs17079773	P-value=4.71E-06 under Additive model for FBAT-PC IA symptoms; P-value=6.60E-06 under Dominant model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs17641078	P-value=4.73E-06 under Additive model for FBAT-PC HI symptoms; P-value=8.44E-06 under Dominant model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs17367118	P-value=8.69E-06 under Additive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs1350666	P-value=8.30E-06 under Additive model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs13353224	P-value=8.54E-06 under Additive model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs1514928	P-value=3.05E-06 under Additive model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs1471225	P-value=8.09E-06 under Additive model for IA symptom count	association finding with P-value association finding with P-value	Trend
rs12679254	P-value=2.08E-06 under Recessive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs1202199	P-value=8.52E-06 under Dominant model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs13330107	P-value=8.50E-06 under Recessive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs130575	P-value=4.67E-06 under Additive model for FBAT-PC all symptoms; P-value=6.20E-06 under Dominant model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs11719664	P-value=2.48E-06 under Additive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs11590090	P-value=2.51E-06 under Recessive model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs11790994	P-value=2.47E-07 under Additive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs11786458	P-value=8.76E-06 under Additive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs478597	P-value=8.08E-06 under Additive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs522958	P-value=1.03E-06 under Recessive model for FBAT-PC all symptoms; P-value=7.59E-07 under Recessive model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs552655	PBAT P-value=0.004, power ranking=2 within inattentive symptoms phenotype in dominant model	achieved significance within a phenotype using the PBAT scre...... achieved significance within a phenotype using the PBAT screening algorithm with various quantitative phenotypes More...	Significant
rs6565113	PBAT P-value=0.005, power ranking=1 within all symptoms phenotype in additive model	achieved significance within a phenotype using the PBAT scre...... achieved significance within a phenotype using the PBAT screening algorithm with various quantitative phenotypes More...	Significant
rs4128767	P-value=1.28E-06 under Dominant model for IA symptom count	association finding with P-value association finding with P-value	Trend
rs41441749	P-value=1.49E-06 under Dominant model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs4147141	P-value=7.90E-06 under Additive model for FBAT-PC IA symptoms;P-value=6.07E-06 under Additive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs4650135	P-value=5.45E-06 under Additive model for FBAT-PC IA symptoms; P-value=6.07E-06 under Dominant model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs260461	P-value=8.38E-06 under Dominant model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs272000	P-value=9.10E-06 under Recessive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs2769967	P-value=3.63E-06 under Recessive model for IA symptom count	association finding with P-value association finding with P-value	Trend
rs363512	P-value=3.89E-06 under Dominant model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs17651978	P-value=6.05E-06 under Recessive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs1918172	P-value=5.18E-06 under Additive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs2014572	P-value=7.32E-06 under Additive model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs2290416	P-value=8.51E-06 under Additive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs930421	P-value=5.64E-06 under Recessive model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs8047014	P-value=3.52E-06 under Additive model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs8041675	P-value=3.98E-06 under Additive model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs7992643	P-value=5.45E-06 under Dominant model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs7816032	P-value=2.25E-06 under Recessive model for HI symptom count	association finding with P-value association finding with P-value	Trend
rs7577925	P-value=2.55E-06 under Dominant model for FBAT-PC all symptoms	association finding with P-value association finding with P-value	Trend
rs7495052	P-value=2.83E-06 under Recessive model for FBAT-PC IA symptoms	association finding with P-value association finding with P-value	Trend
rs7172689	P-value=3.86E-06 under Additive model for IA symptom count; P-value=1.50E-06 under Dominant model for IA symptom count	association finding with P-value association finding with P-value	Trend
rs708188	P-value=7.21E-06 under Recessive model for FBAT-PC all symptoms; P-value=2.17E-06 under Recessive model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs6808138	P-value=5.38E-06 under Additive model for FBAT-PC HI symptoms; P-value=8.21E-06 under Dominant model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend
rs6791644	P-value=8.32E-06 under Recessive model for Total ADHD symptom count	association finding with P-value association finding with P-value	Trend
rs6719977	P-value=1.67E-06 under Additive model for FBAT-PC HI symptoms	association finding with P-value association finding with P-value	Trend

Genes reported by this study (count: 19)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLCO3A1	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
EREG	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
NCKAP5	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
CLYBL	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
NAPRT1	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
ZNF423	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
OXER1	2 flanking SNPs of this gene with P-value<1E-5. 2 flanking SNPs of this gene with P-value<1E-5.	Trend
FHIT	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
IL16	2 flanking SNPs of this gene with P-value<1E-5. 2 flanking SNPs of this gene with P-value<1E-5.	Trend
CDH13	rs6565113 in in this gene was significant within a phenotype...... rs6565113 in in this gene was significant within a phenotype. More...	Significant
FOXP1	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
HAS3	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
ZNF805	2 flanking SNPs of this gene with P-value<1E-5. 2 flanking SNPs of this gene with P-value<1E-5.	Trend
ZNF544	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
MEIS2	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
GFOD1	rs552655 in in this gene was significant within a phenotype. rs552655 in in this gene was significant within a phenotype.	Significant
LPL	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
GRIK1	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend
DMRT2	1 flanking SNPs of this gene with P-value<1E-5. 1 flanking SNPs of this gene with P-value<1E-5.	Trend