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	Guimaraes AP, 200716958038
Citation	Guimaraes A. P., Zeni C., Polanczyk G. V., Genro J. P., Roman T., Rohde L. A. and Hutz M. H. (2007) "Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian sample: preferential transmission of the HTR2A 452His allele to affected boys." Am J Med Genet B Neuropsychiatr Genet, 144B(1): 69-73.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	243 families
Predominant Ethnicity	Caucasian
Population	Brazil
Gender	82.6% of patients were males
Age Group	Children/Adolescents : mean age 10.32 years (SD=3.13)

Detail Info

Summary	In the present study, they investigated a polymorphism in the promoter region of the serotonin transporter (SLC6A4) and two polymorphisms (-1438 A>G and His452-Tyr) in the serotonin 5-HTR2A receptor gene using family based association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No linkage disequilibrium between the two HTR2A polymorphisms was detected in this sample (P-value=0.76). Considering several evidences from animal models for sexual dimorphism in serotonin genes expression, analyses were performed separately for the whole sample and for male probands. No evidences for biased transmissions of both HTR2A -1438 A>G and SLC6A4 polymorphisms to ADHD youths were observed. Preferential transmission of the HTR2A His452 allele was observed only in families with affected boys (P-value=0.04). Their results suggest that findings from ADHD association studies for serotonin genes might be understood inthe context of a gender effect,which may help to explain conflicting results in these association studies.
Total Sample	The sample included 243 families comprising 186 parent proband trios and 57 parent-child duos. Most of them presented the combined type (65.6%), and oppositional defiant disorder was the most common comorbid condition
Sample Collection	Families of children with diagnosed ADHD were recruited from the Child and Adolescent Psychiatric Division of the Hospital de Clinicas de Porto Alegre (HCPA). The ADHD patients were predominantly from European descent (92.1%),
Diagnosis Description	A consensus diagnosis of ADHD based on DSM-IV criteria was achieved through a three-stage process, described in detail previously [Roman et al., 2001; Rohde, 2002].
Technique	DNA was extracted from whole blood lymphocytes by a salting out procedure as already described [Lahiri and Nurnberger, 1991]. The polymorphism at the SLC6A4 promoter was amplified using the polymerase chain reaction (PCR) adapted from Seeger et al. [2001] and Manor et al. [2001]. The HTR2A -1438 A>G and His452Tyr polymorphisms were carried out using the primers and methods described, respectively, by Arranz et al. [1998] and Ozaki et al. [1996].
Analysis Method	Allele frequencies were estimated by counting. Haplotypes and linkage disequilibrium (D) were estimated using the ARLEQUIN software (version 2.000) Dmax and D' values were calculated as described by Lewontin [1988]. For family based association analyses they used the haplotype relative risk (HRR) statistics. Both trios composed of father, mother, and affected child and parent/proband pairs were included in the HRR analyses. Hetero-zygous parent/proband pairs with the same genotype were excluded since the transmission status of parental alleles could not be determined. The statistical package Transmit was also used to test for biased transmission of alleles as well as to test for evidence of association with haplotypes at the HTR2A (-1438 A>G and His452Tyr polymorphisms) gene. Odds ratio estimates were performed with the PEPI statistical program Version 4.0 (Abramson and Gahlinger, 2001). A significance level of 5% was accepted in all comparisons.
Result Description	Allele frequencies for all markers did not show any significant deviation from those expected according to Hardy-Weinberg equilibrium. No evidences for biased transmission of alleles for both HTR2A -1438A>G and SLC6A4 polymorphisms to the ADHD probands were observed. However, a trend for association between the HTR2A His452Tyr polymorphismand ADHD was detected. Preferential transmission of the His452 allele was observed in families with affected boys. Biased transmission of this polymorphism in female probands were different from those observed in boys. No effect of the His452 allele was detected in the sample of girls. No linkage disequilibrium between the two HTR2A markers was detected. Therefore, no specific haplotype was preferentially transmitted to affected children.

Other variant reported by this study (count: 3)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
5HTTLPR	short/long		HRR P-value=0.53 (OR=1.1[0.82-1.45]) in total samples; HRR P...... HRR P-value=0.53 (OR=1.1[0.82-1.45]) in total samples; HRR P-value=0.14 (OR=1.25[0.92-1.71]) in boys samples. More...	No evidences for biased transmission of alleles for this polymorphism to the ADHD probands were observed	Non-significant
HTR2A promoter 1438G/A	G/A		HRR P-value=0.83 (OR=0.97[0.73-1.30]) in total samples; HRR ...... HRR P-value=0.83 (OR=0.97[0.73-1.30]) in total samples; HRR P-value=0.81 (OR=0.96[0.70-1.33]) in boys samples. More...	No evidences for biased transmission of alleles for this polymorphism to the ADHD probands were observed	Non-significant
HTR2A His452Tyr	His/Tyr		HRR P-value=0.07 (OR=1.53[0.93-2.53]) in total samples; HRR ...... HRR P-value=0.07 (OR=1.53[0.93-2.53]) in total samples; HRR P-value=0.04 (OR=1.7[0.99-2.97]) in boys samples. More...	a trend association between this polymorphism and ADHD was detected	Significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLC6A4	No evidences for biased transmission of the allele for SLC6A...... No evidences for biased transmission of the allele for SLC6A4 polymorphism to the ADHD probands were observed. More...	Non-significant
HTR2A	a trend association between a polymorphism in this gene and ...... a trend association between a polymorphism in this gene and ADHD was detected. More...	Significant