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	Manor I, 200111425009
Citation	Manor I., Eisenberg J., Tyano S., Sever Y., Cohen H., Ebstein R. P. and Kotler M. (2001) "Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder." Am J Med Genet, 105(1): 91-5.
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	98 families, about 1000 normal subjects of available genotype
Predominant Ethnicity	Ashkenazi Jews (45%), non-Ashkenazi Jews (34%), mixed (22%)
Population	Israel
Gender	82 males, 16 females
Age Group	Children/Adolescents : 5-17 years (average age: 9.74, SD=2.66)

Detail Info

Summary	Toward unraveling a possible role of the 5-HTTLPR polymorphism in childhood disruptive behaviors, they examined this gene in attention deficit hyperactivity disorder (ADHD), a heterogeneous childhood disorder in which three phenotypes are recognized by DSM IV criteria: inattentive (type I), hyperactive-impulsive (type II), and combined type (type III). By using the haplotype relative risk design, a group of 98 triads (both parents and proband child) were tested for a possible association between 5-HTTLPR and ADHD. A significant decrease in the short/short 5-HTTLPR genotype was observed in the ADHD type III combined group compared with the HRR-derived control group. Similar results were observed when allele frequencies were compared. These first findings should be interpreted cautiously until replicated in independently recruited clinical samples.
Total Sample	ADHD subjects and their families were recruited for participation in this study from two child psychiatry units in Jerusalem (n=45 families) and in the greater Tel Aviv (Petak Tikvah) municipal area (n=53 families). The probands consisted of 82 males and 16 females from 98 families. The nonscreened controls represent a group of subjects recruited for normal personality studies in progress in our laboratory [Auerbach et al.., 1999; Benjamin et al.., 1999a; Benjamin et al.., 1999b; Ebstein et al.., 1997; Ebstein et al.., 1998].
Sample Collection	ADHD subjects and their families were recruited for participation in this study from two child psychiatry units in Jerusalem (n=45 families) and in the greater Tel Aviv (Petak Tikvah) municipal area (n=53 families).
Diagnosis Description	Probands recruited in the Jerusalem area used DSM IV criteria for ADHD according to the K-SAD-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [Shanee, 1966]). The first informant on the probands behavior was the mother who was interviewed by using the K-SAD-PL. The second informant (the teacher) used the Conners Teacher Rating Scale [Conners, 1998] to evaluate the proband's behavior. The percentage of probands with ADHD combined type was 72.3%, inattentive 22.3%, and 5.3% impulsive.
Technique	The 5-HTTLPR-promoter region polymorphism was characterized as previously described by our laboratory [Ebstein et al., 1997]. Polymerase chain reaction (PCR) amplification was performed by using Pfu exo-minus polymerase (Stratagene) and a high denaturing temperature (98^oC).
Analysis Method	All statistical tests were performed by using SPSS for Windows. The haplotype relative risk (HRR) design is based on the article of Falk and Rubenstein [Falk and Rubenstein, 1987] as described by Ewens and Spielman [Ewens and Spielman, 1995] and recently applied by Swanson and his colleagues [Swanson et al., 1998] to a study in ADHD.
Result Description	A significant decrease in the short/short 5-HTTLPR genotype was observed in the ADHD type III combined group (10.29% vs. 30.88%) compared with the HRR-derived control group (likelihood ratio=9.62, P=0.008, n=68 triads). Similar results were observed when allele frequencies were compared (likelihood ratio=3.81, P=0.05, n=136 alleles). These first findings should be interpreted cautiously until replicated in independently recruited clinical samples.

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
5HTTLPR	short/long		genotypic HRR P-value=0.11, likelihood ratio=4.45 in the ADH...... genotypic HRR P-value=0.11, likelihood ratio=4.45 in the ADHD group, genotypic HRR P-value=0.008, likelihood ratio=9.62 in the combined triads, genotypic HRR P-value=0.004, likelihood ratio=11.25 in the ADHD subjects excluding the inattentive group; allelic HRR P-value=0.31, likelihood ratio=1.03 in all ADHD traids, allelic HRR P-value=0.069, likelihood ratio=3.81 in the combined type; HRR P-value=0.108, likelihood ratio=4.45 in the case-control analysis More...	there was a decreased homozygosity of the short/short genotype in the ADHD group but not significant; a significant decrease in homozygosity of the short/short 5-HTTLPR genotype was observed in the ADHD group compared with the HRR control group in the combined traids and in ADHD subjects excluding the inattentive group; no significant differences in 5-HTTLPR allele frequency were observed in all ADHD triads and the ADHD combined type, and a deficit of the short 5-HTTLPR allele in the ADHD group was observed; statistical significance of genotype frequencies was not obtained using a case-control design	Significant

Genes reported by this study (count: 1)