Family-based genome-wide association scan of attention-deficit/hyperactivity disorder.
paper
Cited
Public
- Authors
- Mick, Eric; Todorov, Alexandre; Smalley, Susan; Hu, Xiaolan; Loo, Sandra; Todd, Richard D; Biederman, Joseph; Byrne, Deirdre; Dechairo, Bryan; Guiney, Allan; McCracken, James; McGough, James; Nelson, Stanley F; Reiersen, Angela M; Wilens, Timothy E; Wozniak, Janet; Neale, Benjamin M; Faraone, Stephen V
- Year
- 2010
- Journal
- Journal of the American Academy of Child and Adolescent Psychiatry
- PMID
- 20732626
- DOI
- 10.1016/j.jaac.2010.02.014
- PMCID
- PMC3730251
OBJECTIVE: Genes likely play a substantial role in the etiology of attention-deficit/hyperactivity disorder (ADHD). However, the genetic architecture of the disorder is unknown, and prior genome-wide association studies (GWAS) have not identified a genome-wide significant association. We have conducted a third, independent, multisite GWAS of DSM-IV-TR ADHD. METHOD: 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. RESULTS: Our smallest p value (6.7E-07) 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 = 6.4E-6). We also conducted gene-based tests of candidate genes identified in the literature and found additional evidence of association with SLC9A9. CONCLUSIONS: We and our colleagues in the Psychiatric GWAS Consortium are working to pool together GWAS samples to establish the large data sets needed to follow-up on these results and to identify genes for ADHD and other disorders.
Quantile-Quantile Plot of Association ResultsObserved results of association results are plotted for 835,136 single nucleotide polymorphisms (SNPs) against the expected distribution under the null hypothesis of no association.
LLM interpretation
This is a Quantile-Quantile (Q-Q) plot comparing the observed $-\log_{10}(p)$ values of 835,136 SNPs against the expected distribution under the null hypothesis. The x-axis represents the expected $-\log_{10}(p)$ and the y-axis represents the observed $-\log_{10}(p)$. The data points closely follow the diagonal reference line for most of the distribution but deviate upward at the higher end, indicating a subset of SNPs with stronger-than-expected associations.
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