Study Report

Basic Info
Reference |
Manor I, 200111425009
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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.
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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)
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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 (98oC). |
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 |
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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...
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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
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
SLC6A4 |
the results showed an association between the 5-HTTLPR polym......
the results showed an association between the 5-HTTLPR polymorphism and ADHD
More...
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Significant
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