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	Pazvantoglu, O.,201323872233
Citation	Pazvantoglu O, Gunes S, Karabekiroglu K, Yegin Z, Erenkus Z, Akbas S, Sarisoy G, Korkmaz IZ, Boke O, Bagci H, Sahin AR (2013) The relationship between the presence of ADHD and certain candidate gene polymorphisms in a Turkish sample. Gene 528: 320-7. doi: 10.1016/j.gene.2013.07.004
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	228 parents of children diagnosed with ADHD and 109 healthy parents as the control group
Predominant Ethnicity
Population	Turkish
Gender	in ADHD (n=120) cases,43.3% males and 56.7% females ;in non-ADHD (n=108) cases,38.9% males and 61.1% females ;in healthy (n=109) controls,36.7% males and 63.3% females .
Age Group	Children/Adults : in ADHD (n=120) cases , mean age 37.82 ,SD=6.14 , median (min-max): 38 (22-53) ;in non-ADHD (n=108) cases , mean age 38.40 ,SD=5.81, median (min-max): 38 ,(28-54);in healthy (n=109) controls , mean age 39.41 ,SD= 6.88, median (min-max):39 (23-58).

Detail Info

Summary	The aim of this study was to investigate the association between ADHD and six polymorphisms in five candidate genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25 (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with ADHD and 109 healthy parents as the control group. The polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays and analyzed using the chi-square test and the multinomial logit model.
Total Sample	One hundred and twenty (n=120) parents of children with ADHD had received a diagnosis of ADHD at some time in their lives (childhood or adulthood) (defined as the ADHD group). Sixty-one of these received a diagnosis of childhood ADHD and 59 of adulthood ADHD. One hundred and eight parents had never received a diagnosis of ADHD at any time in their lives (defined as the Non-ADHD group). The HC group underwent the diagnostic procedures described for the study groups; five individuals met the study criteria for ADHD (childhood or adulthood), and 14 had a current psychiatric diagnosis (8 major depressive disorders, 3 obsessive compulsive disorder, 2 panic disorders, and 1 dysthymia).
Sample Collection	Biological parents of children diagnosed with ADHD, treated and followed up during the 1-year study period at the Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ondokuz Mayis University, comprised the study sample. A healthy control group (n = 109) was established consisting of one participant only from families of hospital staff and their relatives who were informed about the study and agreed to participate. All subjects were of Turkish origin and from the Black Sea coastal region.
Diagnosis Description	The parents underwent a psychiatric assessment using the Turkish version of the Structured Clinical Interview for the DSM-IV-TR (SCID-I) (Corapcloglu, 1999) conducted by a psychiatrist and lasting approximately 45 min. Exclusion criteria included other active Axis I psychiatric diseases, mental retardation, history of psychotic disorders, bipolar disorder or substance abuse disorder, neurological disease, or any known genetically transmitted disease. Additionally, we used three self-report measures to assess ADHD symptoms. The Turkish version of the Wender-Utah Rating Scale-25, a 5-point Likert scale based on Utah criteria, was used to evaluate childhood ADHD symptoms retrospectively. The Turkish versions of the Current Symptom Scale (CSS) and Adult ADHD Self-Report Scale (ASRS) were used to evaluate current adulthood ADHD symptoms.
Technique	The polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis using methods previously described elsewhere.
Analysis Method	"Diagnostic groups and demographic and psychometric test variables were analyzed using one-way ANOVA. Significant differences between

SNPs reported by this study (count: 6)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs4818	G/C		genotype: (GG vs GC vs CC), chi-square tests, P-value=0.372, X²=4.258; allele: chi-square tests, P-value=0.174, X²=3.494 among the groups	No significant difference was observed between the groups in...... No significant difference was observed between the groups in terms of allele frequencies for COMT (rs4818). More...	Non-significant
rs2242447	C/T		genotype: (CC vs CT vs TT), chi-square tests, P-value=0.008, X²=13.888; allele: chi-square tests, P-value=0.013, X²=8.700 among groups; genotypic P-value=0.019, allelic P-value = 0.003, X²=8.694, df=1 between the ADHD and the Non-ADHD groups; Presence of the C allele (CC + CT): P-value=0.014, X²=8.581, df=2, among the groups; X²= 7.125, df = 1, P-value = 0.008 between the ADHD and the Non-ADHD groups; Presence of the T allele (TT + CT): X²=6.229, df=2, P-value = 0.044, correction P-value>0.017 among the groups	A significant difference was determined between the groups f...... A significant difference was determined between the groups for NET1 (rs2242447). The significant difference for NET1 (rs2242447) was between the ADHD and Non-ADHD groups. The C allele had a higher frequency in the ADHD group, and the T allele in the Non-ADHD group. There were no differences in allele frequencies for NET1 (rs2242447) between the Non-ADHD and HC groups, or the ADHD and HC groups, after the Bonferroni correction. The NET1 (rs2242447) C allele presence was significantly lower in the Non-ADHD group compared to both the ADHD and HC groups. There was no significant difference in terms of allele presence between the ADHD and HC groups after the Bonferroni correction. Nevertheless, while there was a statistically significant difference in the rates of allele presence of the NET1 (rs2242447) T allele in three-group comparison, there was no significant difference in two-group comparisons after the Bonferroni correction. More...	Significant
rs6311	A/G		genotype: (AA vs AG vs GG ), chi-square tests, P-value=0.117, X²=7.379; allele: chi-square tests, P-value=0.042, X²=6.339 among the groups; allelic P-value = 0.012, X²=6.315, df = 1, between the ADHD and the HC groups; Presence of the A allele (AA + AG): P-value=0.028, X²=7.187, df = 2 among the groups; P-value = 0.007, X² =7.201, df = 1, between the ADHD and HC groups; Presence of the G allele (GG + AG); X² =1.813, P-value =0.014 among the groups	A significant difference was determined between the groups f...... A significant difference was determined between the groups for 5-HT2A (rs6311). 5-HT2A (rs6311) exhibited a significant difference between the ADHD and HC groups. There were no differences in allele frequencies of 5-HT2A (rs6311) between the ADHD and Non-ADHD groups, and the Non-ADHD and HC groups, after the Bonferroni correction. The 5-HT2A (rs6311) G allele exhibited no significant difference among the groups, while A allele presence was significantly higher in the ADHD group than in the HC group. There were no differences in rates of A allele presence between the ADHD and Non-ADHD groups, and the Non-ADHD and HC groups, after the Bonferroni correction. More...	Significant
rs1051312	C/T		genotype: (CC vs CT vs TT), chi-square tests, P-value=0.279, X²=5.084; allele: chi-square tests, P-value=0.692, X²=0.736 among the groups	No significant difference was observed between the groups in...... No significant difference was observed between the groups in terms of allele frequencies for SNAP-25 (rs1051312). More...	Non-significant
rs3746544	G/T		genotype: (GG vs GT vs TT), chi-square tests, P-value=0.003, X²=16.290; allele: chi-square tests, P-value=0.020, X²=7.833 among the groups; genotypic P-value=0.001, X²=13.049, df = 2 between the ADHD and HC groups, P-value=0.017 between the Non-ADHD and HC groups; allelic P-value= 0.009, X²=6.884, df=1 between the ADHD and HC groups; Presence of the G allele (GG + GT): P-value=0.605, X²=1.005, df=2 among the groups; Presence of the T allele (TT + GT): P-value=0.0001, X²=20.845, df=2 among the groups, P-value=0.0001, X² = 16.206, df = 1 between both the ADHD and HC groups, P-value=0.001, X² = 10.641, df = 1 between the Non-ADHD and HC groups	A significant difference was determined between the groups f...... A significant difference was determined between the groups for SNAP-25 (rs3746544). SNAP-25 (rs3746544) exhibited a significant difference between the ADHD and HC groups. T allele frequency was higher in parents with children with ADHD compared with the HC group, while G allele frequency was higher in the HC group. There were no differences in allele frequencies for SNAP-25 (rs3746544) between the ADHD and Non-ADHD groups, or the Non- ADHD and HC groups , after the Bonferroni correction. For SNAP-25 (rs3746544), while the G allele presence exhibited no significant difference among the groups, the presence of the T allele in the ADHD and non-ADHD groups was higher than that in the HC group. In contrast, there was no significant difference in terms of the presence of the G or T alleles between the ADHD and the Non-ADHD groups. More...	Significant
rs6332	A/G		genotype: (AA vs AG vs GG),chi-square tests, P-value=0.463, X²=3.596; allele: chi-square tests, P-value=0.445, X²=1.621 among the groups	No significant difference was observed between the groups in...... No significant difference was observed between the groups in terms of allele frequencies for NTF3 (rs6332). More...	Non-significant

Genes reported by this study (count: 5)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
HTR2A	5-HT2A is significant associated with ADHD in this study. 5-HT2A is significant associated with ADHD in this study.	Significant
NTF3	The SNP in the genes NTF3 (rs6332) was not associated with A...... The SNP in the genes NTF3 (rs6332) was not associated with ADHD More...	Non-significant
COMT	The SNP in the genes COMT (rs4818) was not associated with A...... The SNP in the genes COMT (rs4818) was not associated with ADHD More...	Non-significant
NET1	SNAP-25 rs3746544 T allele and the NET1 rs2242447 C allele: ...... SNAP-25 rs3746544 T allele and the NET1 rs2242447 C allele: P-value=0.007, X²=9.963, df=2 among groups; P-value=0.009, X²=6.901, df=1 between the ADHD and HC groups; P-value=0.005, X²=7.997, df=1 between the ADHD and the Non-ADHD groups. Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25 (rs3746544) is a risk factor for ADHD. More...	Significant
SNAP25	SNAP-25 rs3746544 T allele and the NET1 rs2242447 C allele: ...... SNAP-25 rs3746544 T allele and the NET1 rs2242447 C allele: P-value=0.007, X²=9.963, df=2 among groups; P-value=0.009, X²=6.901, df=1 between the ADHD and HC groups; P-value=0.005, X²=7.997, df=1 between the ADHD and the Non-ADHD groups. We found that even if variation in the SNAP-25 gene alone does not affect the phenotype, it may nevertheless lead to the emergence of a clinical ADHD picture in the presence of other genetic factors. Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25 (rs3746544) is a risk factor for ADHD. Problems associated with the noradrenergic and serotonergic systems and SNAP-25 may play a role, both alone and in interaction with one another, in the pathophysiological mechanisms of ADHD. More...	Significant