| Summary |
The objectives of this study were to: (i) expand their original investigation of the relationship between the HTR1B receptor gene and attention deficit/hyperactivity and; (ii) to investigate a possible association of obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families with an ADHD proband. Six single nucleotide polymorphisms (SNPs) of the HTR1B receptor gene were genotyped using standard methods. Evidence for an association between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive and hyperactive-impulsive quantitative traits was not supported by either TDT single marker analysis or haplotype analysis. In addition they did not find evidence to suggest an association between HTR1B and perfectionism in this sample of ADHD families. |
| Total Sample |
The study sample consisted of 203 nuclear families (55 single parent, 148 two parent families) identified through a proband with a confirmed diagnosis of ADHD. In addition to the probands and parents, 48 affected siblings were genotyped. Based on DSM-IV classification 122 (60%) of the probands were considered ADHD-combined type, 53 (26%) predominantly inattentive type and 28 (14%) predominantly hyperactive-impulsive subtype. Obsessive compulsive behaviors were present in 32 probands, of which 14 (7%) met criteria for OCD. |
| Sample Collection |
The majority of the families reported their ethnic background to be of European Caucasian descent,while 10% of families were of other or mixed background, including Chinese, African, Indian, and Native-Canadians. |
| Diagnosis Description |
The sample originated from consecutive ambulatory referrals for assessment of attention, learning, and behavioral problems to the outpatient clinic of a pediatric hospital in a large metropolitan area. Assessment procedure and diagnostic criteria for inclusion in this study have been described in detail previously [Barr et al., 1999]. In brief, probands met the DSM-IV Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [Association, 1994] criteria for ADHD. Excluded from the study were those children who scored below 80 on both the Performance and Verbal Scales of the WISCIII (Weschsler Intelligence Scale for Children, 3rd Edition), exhibited neurological or chronic medical illness, Tourette Syndrome, chronic multiple tics, bipolar affective disorder, psychotic symptoms or other anxiety, depressive or developmental disorder that might better account for their behavioral symptoms. Children with a family history of bipolar disorder or schizophrenia were also excluded from participation. Please refer to the original publication for more details about Diagnoses of ADHD and comorbid conditions. |
| Technique |
DNA was extracted from blood lymphocytes using a standard high-salt extraction method [Miller et al., 1988]. A total of six single nucleotide polymorphisms (SNPs) were genotyped for this study. The rs6296 (C861G) marker was typed by restriction enzyme (HincII); the remaining polymorphisms were genotyped using the 50 nuclease assay (TaqMan1 on an ABI 7900 (Applied Biosystems, Foster City, CA). Markers rs6298 and rs6297 were typed using Taqman MGB probes; andmarkers rs1213371, rs130058, and rs200292 were typed using assay-on-demand. Reference information of primers, probes, and flanking sequences are detailed in original publication. Plates were read on the ABI 7900 HT Sequence Detection Systemusing allelic discrimination end-point analysismode of the software package version 2.0 (Applied Biosystems). |
| Analysis Method |
The transmission disequilibrium test (TDT) was performed using the extended transmission disequilibrium test program [Sham and Curtis, 1995]. Transmission of haplotypes was analyzed with the TRANSMIT program [Clayton, 1999]. Quantitative analysis of haplotypes was estimated using FBAT [Horvath et al., 2001] |
| Result Description |
No evidence for biased transmission for any of the selected markers was found. No evidence for either paternal- ormaternal-biased transmission was found. No evidence of biased transmission of any of the five most common haplotypes and ADHD as a categorical trait. Quantitative analysis of the inattentive and hyperactive-impulsive traits also revealed no evidence for biased transmission for any of the selected markers. No evidence for biased transmission of any of the selected markers and perfectionism and the most common haplotypes when exploring the relationship between HTR1B and OCD traits in sample using the parent and teacher report of the CPRS-R subscale E-perfectionism as quantitative traits. |
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