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

Study Report

Basic Info

Reference	Smalley SL, 200212187510
Citation	Smalley S. L., Kustanovich V., Minassian S. L., Stone J. L., Ogdie M. N., McGough J. J., McCracken J. T., MacPhie I. L., Francks C., Fisher S. E., Cantor R. M., Monaco A. P. and Nelson S. F. (2002) "Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism." Am J Hum Genet, 71(4): 959-63.
Study Design	affected sib pairs
Study Type	Linkage study
Sample Size	277 ASPs
Predominant Ethnicity	Caucasian
Population	USA
Gender	322 male and 118 female
Age Group	Children/Adolescents : mean age of 11 years

Detail Info

Summary	They uses affected-sib-pair analysis in 203 families to localize the first major susceptibility locus for ADHD to a 12-cM region on chromosome 16p13, building upon an earlier genomewide scan of this disorder. The region overlaps that highlighted in three genome scans for autism, a disorder in which inattention and hyperactivity are common, and physically maps to a 7-Mb region on 16p13. These findings suggest that variations in a gene on 16p13 may contribute to common deficits found in both ADHD and autism.
Total Sample	The sample used in the present study consists of 277 affected sib pairs (ASPs) in 203 families, including 126 ASPs (104 families) from the previous genomewide scan of ADHD (Fisher et al. 2002).
Sample Collection	The affected members (322 male and 118 female) in the ASPs were largely white (80%).
Diagnosis Description	ADHD was diagnosed using DSM-IV criteria, with 95% of affected individuals meeting full criteria and 5% of affected individuals falling one symptom short but meeting age-at-onset and impairment criteria (USAn Psychiatric Association 1994). This definition of ADHD corresponds to the broad classification used in the previous ge-nomewide scan (Fisher et al. 2002). All families with ASP had at least one affected member meeting full criteria (for a description of the measures and diagnostic methods, see Smalley et al. 2000). The affected members in the ASPs had a mean IQ of 106.
Technique	Individuals were genotyped for 11 microsatellites and 5 SNPs spanning ~25 cM on chromosome 16p, analyzed using standard procedures (Hirschhorn et al. 2000; Fisher et al. 2002). Both parents were genotyped in 185 (91%) of the families, and only one parent was genotyped in 18 (9%) of the families.
Analysis Method	Single and multipoint maximum LOD scores (MLSs) were computed under the possible triangle method, under the assumption of no dominance variance, through use of ASPEX. Transmission/disequilibrium testing (TDT) of the SNPs and ADHD was performed using ASPEX, which allows for multiple siblings to be included in a test of association in the presence of linkage, by permuting parental alleles while fixing the identity-by-descent (IBD) status of the siblings.
Result Description	Significant linkage was observed for ADHD and the markers on 16p, with the maximum obtained near marker D16S3114. The 1-LOD support interval falls between markers D16S519 and D16S405, within estimated distances of ~12 cM in current data set and ~7 Mb on the basis of physical maps (HGP-sc and CEL) of the region between these two markers. The significant linkage in the extended sample was a function of both the increased density of markers and the additional ASPs. In the initial genome scan, the linkage finding for markers on chromosome 16 and ADHD (~10-cM density) was a multipoint MLS of 1.5 near marker D16S3075 (Fisher et al. 2002). The markers in the present analyses (~2-cM density) yielded a multipoint MLS of 3.1 at marker D16S3114 in the same set of ASPs, despite similar levels of marker heterozygosity (i.e., the average information content of the first set was 79%, and that of the second set was 81%). The additional set of 153 ASPs independently yielded a multipoint MLS of 1.9.

Regions reported by this study (count: 1)