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	Neale BM, 200818980221
Citation	Neale B. M., Lasky-Su J., Anney R., Franke B., Zhou K., Maller J. B., Vasquez A. A., Asherson P., Chen W., Banaschewski T., Buitelaar J., Ebstein R., Gill M., Miranda A., Oades R. D., Roeyers H., Rothenberger A., Sergeant J., Steinhausen H. C., Sonuga-Barke E., Mulas F., Taylor E., Laird N., Lange C., Daly M. and Faraone S. V. (2008) "Genome-wide association scan of attention deficit hyperactivity disorder." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1337-44.
Study Design	family-based
Study Type	GWAS
Sample Size	958 trios
Predominant Ethnicity	Caucasian
Population	Belgium, Germany, Ireland, Israel, the Netherlands, Spain, Switzerland, United Kingdom
Gender	119 female, 790 male
Age Group	Children/Adolescents : aged 5-17

Detail Info

Summary	To search for ADHD susceptibility genes, they genotyped approximately 600,000 SNPs in 958 ADHD affected family trios. After cleaning the data, they analyzed 438,784 SNPs in 2,803 individuals comprising 909 complete trios using ADHD diagnosis as phenotype. They present the initial TDT findings as well as considerations for cleaning family-based TDT data. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. They additionally identify a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.
Total Sample	A total of 958 affected proband-parent trios were initially selected for the GWAS scan. 2,803 individuals comprising 909 complete trios were left after data cleaning.
Sample Collection	Family members were primarily of Western European origin hailing from eight countries including Belgium, Germany, Ireland, Israel, the Netherlands, Spain, Switzerland, and the United Kingdom.
Diagnosis Description	Prior to entry into the study, all probands underwent clinical evaluations by a pediatrician or child psychiatrist and both existing and new patients were included in the study. Patients had to meet clinical criteria for ADHDcombined type before being enrolled in the study. Wherever possible, families withdrew stimulant medication for 1 week prior to research assessments to allow for more accurate ascertainment of the current level of ADHD symptoms and behaviors. Alternatively we ensured as far as possible that ratings were based on medication free periods. Probands were excluded from the study if the last medication free period was more than 2 years ago. For more details please refer to the original publication.
Technique	Genotyping was conducted at Perlegen Sciences using their 600 K genotyping platform, which comprises approximately 600,000 tagging SNPs designed to be in high linkage disequilibrium with untyped SNPs for the three HapMap populations. The DNA was extracted from blood for all samples and stored at the Rutgers depository. Genotype data were cleaned by The National Center for Biotechnology Information (NCBI). Quality Control analyses were processed using the GAIN QA/QC Software Package (version 0.7.4) developed by Goncalo Abecasis and Shyam Gopalakrishnan at the University of Michigan.
Analysis Method	They used the transmission disequilibrium test (TDT) as implemented in PLINK. To determine the quality of the genotype calling in the top of the distribution, they also inspected the cluster plots of the intensity for the genotypes. In addition to performing the basic TDT, they attempted to identify any sources of potential bias, by attempting to predict the TDT chi-square test statistic as a function of major versus minor allele overtransmission at the locus. They also explored the existing candidate genes from the ADHD literature, to place the potential effects in context. The approach for dealing with multiple testing is to require genome-wide association significance to assert that a putative finding is a true positive.
Result Description	After the quality control procedures, 438,784 markers were adequate for use in the statistical analyses. TDT analysis was restricted to a subset of 909 complete family trios to prevent bias in the association statistic. None of the SNP association tests achieved genome-wide significance, indicating that larger samples may be required to identify risk loci for ADHD. They additionally identified a systemic bias in family-based association, and suggest that variable missing genotype rates may be the source of this bias.

SNPs reported by this study (count: 36)

SNP	Allele Change	Statistical Values	Author Comments	Result of Statistical Analysis
rs964647	T:A	Uncorrected TDT P-value=1.50E-05 (OR=1.717); Corrected TDT P-value=1.34E-05 (OR=1.717)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs9676447	C:T	Uncorrected TDT P-value=1.14E-05 (OR=2.078); Corrected TDT P-value=1.01E-05 (OR=2.078)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs9973180	T:C	Uncorrected TDT P-value=7.05E-05 (OR=0.7489)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs10807124	A:G	Uncorrected TDT P-value=6.71E-05 (OR=0.7435)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs12772737	G:C	Corrected TDT P-value=4.96E-05 (OR=0.7246)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs1427324	T:C	Uncorrected TDT P-value=1.75E-05 (OR=0.7236); Corrected TDT P-value=3.50E-05 (OR=0.7236)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs11221064	C:G	Corrected TDT P-value=3.89E-05 (OR=1.439)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs12505502	G:T	Uncorrected TDT P-value=6.21E-05 (OR=1.303); Corrected TDT P-value=5.62E-05 (OR=1.303)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs17673653	T:A	Uncorrected TDT P-value=4.32E-05 (OR=0.6612)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs17689952	G:A	Uncorrected TDT P-value=4.16E-05 (OR=0.7219)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs1539549	T:C	Uncorrected TDT P-value=1.42E-05 (OR=0.7305); Corrected TDT P-value=2.88E-05 (OR=0.7305)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs1541665	T:C	Corrected TDT P-value=5.60E-05 (OR=0.6338)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs2295426	C:T	Corrected TDT P-value=1.00E-05 (OR=0.7103)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs2311120	G:A	Corrected TDT P-value=1.22E-05 (OR=0.6795)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs17722514	T:C	Corrected TDT P-value=3.14E-05 (OR=1.648)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs17754282	G:T	Uncorrected TDT P-value=5.51E-05 (OR=1.441); Corrected TDT P-value=4.97E-05 (OR=1.441)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs2678787	C:T	Corrected TDT P-value=6.36E-05 (OR=0.7228)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs2747100	G:C	Uncorrected TDT P-value=5.66E-05 (OR=0.7637)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs2323262	A:G	Uncorrected TDT P-value=6.10E-05 (OR=0.697)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs2439832	T:C	Uncorrected TDT P-value=4.66E-05 (OR=0.6567)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs4913069	A:G	Uncorrected TDT P-value=6.94E-05 (OR=0.6476)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs4241112	T:C	Uncorrected TDT P-value=3.16E-05 (OR=0.7214); Corrected TDT P-value=6.06E-05 (OR=0.7214)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs3782309	T:G	Uncorrected TDT P-value=6.11E-05 (OR=1.527); Corrected TDT P-value=5.53E-05 (OR=1.527)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs2939678	A:G	Uncorrected TDT P-value=3.87E-05 (OR=0.7222)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs7187223	G:A	Corrected TDT P-value=5.21E-05 (OR=0.4458)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs6919857	C:T	Uncorrected TDT P-value=2.46E-05 (OR=0.749); Corrected TDT P-value=4.79E-05 (OR=0.749)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs6657749	T:C	Corrected TDT P-value=2.99E-05 (OR=0.6643)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs6570426	T:A	Corrected TDT P-value=2.74E-05 (OR=0.735)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs922781	C:G	Uncorrected TDT P-value=6.20E-05 (OR=1.315); Corrected TDT P-value=5.62E-05 (OR=1.315)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs876477	T:C	Uncorrected TDT P-value=2.99E-05 (OR=1.903); Corrected TDT P-value=2.69E-05 (OR=1.903)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs7657608	T:C	Uncorrected TDT P-value=3.30E-05 (OR=1.356); Corrected TDT P-value=2.96E-05 (OR=1.356)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs7528615	C:T	Uncorrected TDT P-value=6.86E-05 (OR=0.7559)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs9608617	C:G	Uncorrected TDT P-value=3.29E-05 (OR=1.376); Corrected TDT P-value=2.96E-05 (OR=1.376)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant
rs957795	A:G	Uncorrected TDT P-value=3.86E-05 (OR=0.619)	One of top 25 results in uncorrected TDT test One of top 25 results in uncorrected TDT test	Non-significant
rs9484448	T:C	Corrected TDT P-value=2.94E-05 (OR=0.7385)	One of top 25 results in corrected TDT test One of top 25 results in corrected TDT test	Non-significant
rs9389835	C:T	Uncorrected TDT P-value=7.45E-06 (OR=0.7307); Corrected TDT P-value=1.58E-05 (OR=0.7307)	One of top 25 results in both uncorrected and corrected TDT ...... One of top 25 results in both uncorrected and corrected TDT test More...	Non-significant