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	Bhaduri N, 201019757024
Citation	Bhaduri N., Sarkar K., Sinha S., Chattopadhyay A. and Mukhopadhyay K. (2010) "Study on DBH genetic polymorphisms and plasma activity in attention deficit hyperactivity disorder patients from Eastern India." Cell Mol Neurobiol, 30(2): 265-74.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	111 probands and their family members; 130 controls for the genetic study and 30 controls for analysis of enzymatic activity
Predominant Ethnicity	Indo-Caucasian
Population	India
Gender	male to female ratio: 10:1
Age Group	Children/Adolescents : 7.37 years (SD=2.72)

Detail Info

Summary	In the present study association of ADHD with four genetic polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152, was examined in subjects belonging to eastern India. ADHD subjects (n = 111) were recruited following DSM-IV criteria. Peripheral blood samples were collected from nuclear families with ADHD probands. A group of ethnically matched healthy volunteers (n = 130) was also recruited. Genomic DNA was analyzed by PCR amplification followed by restriction digestion and genotyping. Data obtained were subjected to both family-based as well as population-based statistical analyses. Plasma DbH activity was measured using a photometric assay and its correlation with the genetic polymorphisms was analyzed using analysis of variance. Case-control analysis revealed no significant differences in allelic frequencies; however, significant paternal over-transmission (P-value= 0.02) of the rs2519152 'G' allele to ADHD probands was noticed. A haplotype, composed of 12R-C-G-G, also showed biased transmission. Strong correlation was observed between enzyme activity and rs1611115, rs1108580, and rs2519152 (P-value= 1.51E-6, 0.04, and 0.003, respectively). The present study hints toward the fact that DBH gene polymorphisms have some role in the etiology of ADHD in eastern Indian population and their study could be useful for therapeutic intervention.
Total Sample	111 probands and their family members were selected from the outpatient department of Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, Kolkata. Out of the 111 families recruited, 98 families were complete parent-proband trios, while 13 families had only one parent and affected proband. Two control groups (healthy volunteers and their children), one group for the genetic study (n = 130; mean age 34.5 years SD= 8.2 ; 1:2 male-to-female ratio) and another age-matched group for analysis of enzymatic activity (n = 30; mean age 8.6 years SD= 2.4 ; 1:1 male-to-female ratio), were also recruited following evaluation by the same psychometric procedure.
Sample Collection	Indo-Caucasoid ethnic category
Diagnosis Description	Families were interviewed by mental health professionals (child psychiatrist and clinical psychologist) using a behavioral questionnaire modeled after the DSM-IV (APA 1994) followed by psychological evaluations through (1) Conners' Parents and Teachers Rating Scale (Conners 1997) for the hyperactivity level and (2) Intelligence Quotient assessment by Wechsler Intelligence Scale for children above 5 years (Wechsler 1991) and Developmental Quotient by Developmental Screening Test for children below 5 years (Bharat Raj 1971). Twelve probands belonged to the inattentive subtype, 23 belonged to the hyperactive/impulsive subtype, and the rest 76 belonged to combined subtype of ADHD.
Technique	Peripheral blood was collected from ADHD subjects, their parents, and control individuals. Genomic DNA was prepared from leUnited Kingdomocytes using the high-salt precipitation protocol (Miller et al. 1988). A 50 flanking (GT)n dinucleotide repeat (DBH-STR) and three SNPs were included for the study.
Analysis Method	Allelic and haplotypic comparisons between case and control group were analyzed using COCAPHASE, which is part of a suite of programs UNPHASED (Dudbridge 2003). Family-based association studies were performed using haplotype-based haplotype relative risk (HHRR) design (Terwilliger and Ott 1992) and transmission disequilibrium test (TDT). Please refer to the original article for more details.
Result Description	Case-control analysis revealed no significant differences in allelic frequencies; however, significant paternal over-transmission (P-value= 0.02) of the rs2519152 'G' allele to ADHD probands was noticed. A haplotype, composed of 12R-C-G-G, also showed biased transmission. Strong correlation was observed between enzyme activity and rs1611115, rs1108580, and rs2519152 (P-value=1.51E-6, 0.04, and 0.003, respectively). The present study hints toward the fact that DBH gene polymorphisms have some role in the etiology of ADHD in eastern Indian population.

SNPs reported by this study (count: 3)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs2519152	A:G		allelic frequencies P-value=0.6, X²=0.27; genotypic frequencies P-value=0.65, X²=0.86; HHRR P-value=0.25, OR=0.74, X²=1.34, TDT P-value=0.22, RR=0.71, X²=1.54 for overall transmission; HHRR P-value=0.03, OR=0.46, X²=4.66, TDT P-value=0.02, RR=0.4, X²=5.31 for paternal transmission; HHRR P-value=0.58, OR=1.23, X²=0.31, TDT P-value=0.55, RR=1.27, X²=0.36 for maternal transmission	showed a statistically significant over-transmission of the ...... showed a statistically significant over-transmission of the ¡®G¡¯ allele from father to probands More...	Significant
rs1108580	G:A		allelic frequencies P-value=0.43, X²=0.6; genotypic frequencies P-value=0.64, X²=0.91; HHRR P-value=0.36, OR=1.27, X²=0.84, TDT P-value=0.37, RR=1.26, X²=0.81 for overall transmission; HHRR P-value=0.46, OR=1.32, X²=0.55, TDT P-value=0.45, RR=1.33, X²=0.57 for paternal transmission; HHRR P-value=0.58, OR=1.23, X²=0.34, TDT P-value=0.6, RR=1.2, X²=0.27 for maternal transmission	no significant association with ADHD no significant association with ADHD	Non-significant
rs1611115	C:T		allelic frequencies P-value=0.4, X²=0.65; genotypic frequencies P-value=0.72, X²=0.65; HHRR P-value=0.88, OR=1.04, X²=0.02, TDT P-value=0.88, RR=1.05, X²=0.02 for overall transmission; HHRR P-value=0.69, OR=0.85, X²=0.16, TDT P-value=0.65, RR=1.22, X²=0.2 for paternal transmission; HHRR P-value=0.55, OR=1.26, X²=0.35, TDT P-value=0.55, RR=1.27, X²=0.36 for maternal transmission	no significant association with ADHD no significant association with ADHD	Non-significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DBH 5'-flanking (GT)n	12R, 13R, 14R		allelic frequencies P-value=0.08, X²=4.85; genoty...... allelic frequencies P-value=0.08, X²=4.85; genotypic frequencies P-value=0.92, X²=0.91; HHRR P-value=0.68, OR=1.18, X²=0.17, TDT P-value=0.69, RR=1.67, X²=0.2 for 14R allele; HHRR P-value=0.35, OR=0.80, X²=0.88, TDT P-value=0.31, RR=0.77, X²=1.03 for 13R allele, HHRR P-value=0.5, OR=1.17, X²=0.5, TDT P-value=0.45, RR=1.21, X²=0.56 for 12R allele for overall transmission; HHRR P-value=0.7, OR=1.37, X²=0.15, TDT P-value=0.71, RR=1.33, X²=0.14 for 14R allele; HHRR P-value=0.13, OR=0.64, X²=2.24, TDT P-value=0.09, RR=0.53, X²=2.84 for 13R allele, HHRR P-value=0.19, OR=1.53, X²=1.7, TDT P-value=0.13, RR=1.8, X²=2.32 for 12R allele for paternal transmission; HHRR P-value=0.81, OR=1.13, X²=0.06, TDT P-value=0.81, RR=1.11, X²=0.05 for 14R allele; HHRR P-value=0.87, OR=1.06, X²=0.03, TDT P-value=0.86, RR=1.06, X²=0.03 for 13R allele, HHRR P-value=0.75, OR=0.9, X²=0.1, TDT P-value=0.74, RR=0.89, X²=0.11 for 12R allele for paternal transmission More...	no significant association with ADHD	Non-significant

Genes reported by this study (count: 1)