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	Mick E, 201020732626
Citation	Mick E., Todorov A., Smalley S., Hu X., Loo S., Todd R. D., Biederman J., Byrne D., Dechairo B., Guiney A., McCracken J., McGough J., Nelson S. F., Reiersen A. M., Wilens T. E., Wozniak J., Neale B. M. and Faraone S. V. (2010) "Family-based genome-wide association scan of attention-deficit/hyperactivity disorder." J Am Acad Child Adolesc Psychiatry, 49(9): 898-905 e3.
Study Design	family-based
Study Type	GWAS
Sample Size	735 trios
Predominant Ethnicity	Caucasian
Population	USA
Gender	472(64%) males
Age Group	Children/Adolescents : aged 6-17, mean age 12.3 years (SD=4.0)

Detail Info

Summary	They have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD. Families were ascertained at Massachusetts General Hospital (MGH; N=309 trios), Washington University at St. Louis (WASH-U; N=272 trios), and University of California at Los Angeles (UCLA; N=156 trios). Genotyping was conducted with the Illumina Human1M or Human1M-Duo BeadChip platforms. After applying quality control filters, association with ADHD was tested with 835,136 SNPs in 735 DSM-IV ADHD trios from 732 families. The smallest p value (6.7E-07) in this study did not reach the threshold for genome-wide statistical significance (5.0E-08), but one of the 20 most significant associations was located in a candidate gene of interest for ADHD (SLC9A9, rs9810857, P-value=6.4E-6). They also conducted gene-based tests of candidate genes identified in the literature and found additional evidence of association with SLC9A9.
Total Sample	735 trios from 732 families, of which 309 trios are from MGH, 272 trios are from WASH-U and 156 trios are from UCLA
Sample Collection	Families were ascertained at Massachusetts General Hospital (MGH; N=309 trios), Washington University at St Louis (WASH-U; N=272 trios), and University of California at Los Angeles (UCLA; N=156 trios). In total, 92% samples are Caucasian origin.
Diagnosis Description	DSM-IV-TR criteria for ADHD require at least six of nine symptoms of inattention and/or hyperactivity impulsivity to be endorsed. Symptoms associated with significant impairment in different settings by 7 years of age. In this study, subjects were not initially identified according to DSM-IV-TR criteria, but only those subjects meeting full diagnostic criteria (of any DSM-IV-TR ADHD subtype) were enrolled in this genome-wide association study. For detailed diagnosis information, please refer to the original publication.
Technique	DNA was extracted from blood at each participating institution and Genizon BioSciences Inc. conducted genotyping with funding from Pfizer Inc. Genomic DNA samples from MGH and WASH-U were genotyped using the Illumina Human1M BeadChip (N= 1,057,265 SNPs), whereas the UCLA samples were genotyped using the Illumina Human 1M-Duo array (N=1,151,846 SNPs). Genotyping calls were generated after clustering all available data within platform at Genizon and then merged into a single file of 1,172,613 SNPs. To generate a data set of markers common to all sites, they removed SNPs that were either not included on both arrays (N=128,718 SNPs) or failed preliminary quality control (QC) procedures conducted at Genizon (99% call rate for all samples and for all SNPs, gender check, Mendelian errors) on both the 1M and 1M-Duo arrays (N=9,500 SNPs), the 1M array only (N=39,753 SNPs) or the 1M-Duo array only (N=11,201 SNPs). Once the data from the multiple sites and different Illumina arrays were merged, there were 983,441 SNPs genotyped across the complete sample of 737 trios.
Analysis Method	PLINK was used to conduct transmission disequilibrium tests. To control for multiple comparisons they adopted the conservative recommendation of Dudbridge et al and Pe¡¯er et al. and considered p values less than 5.0E-08 to be statistically significant genome-wide. They also examined 43 candidate genes (N=3,603 SNPs) of interest. They used the set-based tests provided in PLINK. Permutation tests were used to obtain empirical significance levels of the gene-based test, while accounting for the number of tests conducted within gene and the lack of independence of SNPs within gene. Sets could comprise up to 5 SNPs, and gene-wide statistical significance was estimated with 50,000 permutations.
Result Description	The smallest P-value (6.7E-07) in this study did not reach the threshold for genome-wide statistical significance (5.0E-08), but one of the 20 most significant associations was located in a candidate gene of interest for ADHD (SLC9A9, rs9810857, P-value=6.4E-6). They also conducted gene-based tests of candidate genes identified in the literature and found additional evidence of association with SLC9A9.

SNPs reported by this study (count: 20)

SNP	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs10120476	T	TDT P-value=1.18E-05 (OR=9)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs10487524	T	TDT P-value=9.12E-06 (OR=1.6)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs10833716	C	TDT P-value=9.66E-06 (OR=0.65)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Trend
rs11074889	A	TDT P-value=6.71E-07 (OR=1.68)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs10011926	A	TDT P-value=8.07E-06 (OR=0.67)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs2602381	A	TDT P-value=3.85E-06 (OR=1.42)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs2823819	C	TDT P-value=6.70E-07 (OR=1.65)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs4132831	A	TDT P-value=1.70E-05 (OR=0.72)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs438259	A	TDT P-value=3.71E-06 (OR=1.49)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs11953346	C	TDT P-value=1.59E-05 (OR=0.71)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs17023218	A	TDT P-value=1.88E-05 (OR=0.68)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs1859156	T	TDT P-value=2.05E-06 (OR=0.65)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs2107654	T	TDT P-value=1.52E-05 (OR=0.72)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs9350410	G	TDT P-value=2.33E-05 (OR=1.39)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs8074751	C	TDT P-value=1.18E-06 (OR=0.69)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs9810857	T	TDT P-value=6.41E-06 (OR=1.41)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs6561686	C	TDT P-value=2.08E-05 (OR=0.47)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs4923705	C	TDT P-value=2.40E-06 (OR=1.51)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results; annotated by GWAS Catalog More...	Trend
rs7702178	G	TDT P-value=1.84E-05 (OR=1.53)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant
rs760609	A	TDT P-value=2.51E-05 (OR=1.37)	One of the top 20 associations from genome-wide association ...... One of the top 20 associations from genome-wide association results More...	Non-significant

Genes reported by this study (count: 22)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
NFIL3	Gene-based set test P-value=0.041. Significant gene-based se...... Gene-based set test P-value=0.041. Significant gene-based set tests of association with selected candidates, but contains no significant or Trend associated SNPs. More...	Significant
CSNK1E	Gene-based set test P-value=0.0038. Significant gene-based s...... Gene-based set test P-value=0.0038. Significant gene-based set tests of association with selected candidates, but contains no significant or Trend associated SNPs. More...	Significant
FADS1	Gene-based set test P-value=0.019. Significant gene-based se...... Gene-based set test P-value=0.019. Significant gene-based set tests of association with selected candidates, but contains no significant or Trend associated SNPs. More...	Significant
BMPR1B	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
SLC9A9	Gene-based set test P-value=0.0017. Significant in gene-base...... Gene-based set test P-value=0.0017. Significant in gene-based set tests of association, and contains Trend associated SNPs. More...	Significant
FADS2	Gene-based set test P-value=0.047. Significant gene-based se...... Gene-based set test P-value=0.047. Significant gene-based set tests of association with selected candidates, but contains no significant or Trend associated SNPs. More...	Significant
ARRB1	Gene-based set test P-value=0.024. Significant gene-based se...... Gene-based set test P-value=0.024. Significant gene-based set tests of association with selected candidates, but contains no significant or Trend associated SNPs. More...	Significant
RBMS3	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
ANO5	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
C21orf34	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
UGT1A9	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
MCTP1	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
RPL31P43	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
RPL23AP56	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
CEP112	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
ATPBD4	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
LECT1	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
DNAJA1P4	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
DUSP1	No significant or Trend associated SNP was mapped in this ge...... No significant or Trend associated SNP was mapped in this gene. More...	Non-significant
ELOVL6	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
LOC643308	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend
EMP2	Trend associated SNP was mapped in this gene. Trend associated SNP was mapped in this gene.	Trend