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Data Summary
Study Report
| Reference | Turic D, 2005(a)15950021 |
|---|---|
| Citation | Turic D., Langley K., Williams H., Norton N., Williams N. M., Moskvina V., Van den Bree M. B., Owen M. J., Thapar A. and O'Donovan M. C. (2005) "A family based study implicates solute carrier family 1-member 3 (SLC1A3) gene in attention-deficit/hyperactivity disorder." Biol Psychiatry, 57(11): 1461-6. |
| Study Design | family-based |
| Study Type | Candidate-gene association study |
| Sample Size | 299 families |
| Predominant Ethnicity | Caucasian |
| Population | United Kingdom |
| Gender | 92% male and 8% female |
| Age Group | Children/Adolescents : 6-16 years old (mean age 9.2 years, standard deviation 1.8 years) |
| Summary | They have undertaken detailed association analysis of SLC1A3 using a multi-stage approach for candidate gene analysis. In a family-based sample (n=299) they found a significant association between marker rs2269272 (p=0.007) and ADHD. Two, two-marker haplotypes, rs2269272/rs3776581 (p=0.016) and rs2269272/rs2032893 (p=0.013) also yielded evidence of association. The results of their study suggest that genetic variation in SLC1A3 may contribute to susceptibility to ADHD. |
|---|---|
| Total Sample | The sample included 299 families comprising 184 parent-proband trios and 115 parent-child duos. ADHD probands, of whom 92% were male and 8% female, were of Caucasian British origin, and were 6-16 years old (mean age 9.2 years, standard deviation 1.8 years) at the time of interview. |
| Sample Collection | Families of children with suspected or diagnosed ADHD were recruited from District Child and Adolescent Psychiatry and Pediatric Clinics in South Wales, Bristol, the South West of United Kingdom and Greater Manchester. |
| Diagnosis Description | Mothers were interviewed about their children, using the Child and Adolescent Psychiatric Assessment (CAPA; Angold et al 1995), a research diagnostic interview. Reports of ADHD symptoms and impairment at school were also obtained using a semi-structured teacher telephone interview (Child ADHD Teacher Telephone Interview-CHATTI; Holmes et al 2004). Diagnoses were assigned according to ICD-10, DSM-IV and DSM-III-R criteria. |
| Technique | DNA was extracted from venous blood or mouthwash samples using standard techniques. SNPs were selected for analysis to cover the whole genomic sequence of SLC1A3 gene (~90 kb) at a density of approximately one SNP per 5 kb (n=18 SNPs). PCR primers were designed using Primer3. Extension primers were designed using our in house software FP PRIMER 1.0.1b available at http://m034.pc.uwcm.ac.United Kingdom/FP_ Primer.html. Polymerase chain reactions (PCRs) were performed under standard conditions in 12 ul reaction volumes containing 20 ng of genomic DNA. For more genotyping details, please refer to the original publication. |
| Analysis Method | Individual genotype data were analyzed for the complete sample (complete parent/child trios and mother/child or father/ child duos) using the statistical package TRANSMIT (Clayton 1999). Evidence for association with haplotypes was sought using the same program. Departures from Hardy-Weinberg equilibrium, allele frequencies, LD and r2 were calculated using Haploview (http://www.genome.wi.mit.edu/personal/jcbarret/ haploview). |
| Result Description | They found a significant association between marker rs2269272 (p=0.007) and ADHD in the family-based sample. Two, two-marker haplotypes, rs2269272/rs3776581 (p=0.016) and rs2269272/rs2032893 (p=0.013) also yielded evidence of association. The results of their study suggest that genetic variation in SLC1A3 may contribute to susceptibility to ADHD. |
| SNP | Allele Change | Risk Allele | Statistical Values | Author Comments | Result of Statistical Analysis |
|---|---|---|---|---|---|
| rs1541815 | A/G | no P-value | no association no association | Non-significant | |
| rs2731886 | A/C | P-value=0.91 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs2032892 | C/G(E219D) | no P-value | no association no association | Non-significant | |
| rs4869686 | A/T | P-value=0.56 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs4591778 | C/T | P-value=0.78 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs3776585 | A/G | P-value=0.20 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs2301064 | C/T | no P-value | no association no association | Non-significant | |
| rs3776568 | C/G | no P-value | no association no association | Non-significant | |
| rs3776581 | A/G | P-value=0.09 for pooled genotyping; allelic TRANSMIT P-value=0.06, X2=3.25 | a trend for association with A allele a trend for association with A allele | Non-significant | |
| rs3776576 | A/C | P-value=0.24 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs930072 | C/T | P-value=0.69 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs1428975 | A/G | P-value=0.21 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs3776579 | G/T | P-value=0.36 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs1862638 | A/T | P-value=0.38 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs3903407 | C/G | P-value=0.28 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs2032893 | A/G | allelic TRANSMIT P-value=0.05, X2=3.71 | produced modest evidence for association, with an excess of ...... produced modest evidence for association, with an excess of transmissions of allele G More... | Non-significant | |
| rs36684 | A/G | no P-value | no association no association | Non-significant | |
| rs2269272 | C/T | P-value=0.08 for pooled genotyping; allelic TRANSMIT P-value=0.007, X2=8.54 | an excess of transmissions of T allele was confirmed an excess of transmissions of T allele was confirmed | Significant | |
| rs2269273 | A/G | no P-value | no association no association | Non-significant | |
| rs1049522 | A/C | P-value=0.60 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs1049524 | A/G | P-value=0.30 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs3733812 | C/T | P-value=0.58 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant | |
| rs4421131 | A/G | P-value=0.19 for pooled genotyping | not significantly associated with ADHD not significantly associated with ADHD | Non-significant |
| Gene | Statistical Values/Author Comments | Result of Statistical Analysis |
|---|---|---|
| SLC1A3 | two marker haplotype (rs3776581/rs2269272) TRANSMIT P-value=...... two marker haplotype (rs3776581/rs2269272) TRANSMIT P-value=0.016, X2(df=3)=10.47; two marker haplotype (rs2269272/rs2032893) TRANSMIT P-value=0.013, X2(df=3)=11.60; Haplotype T/G of rs2269272/rs2032893 P-value=0.003, X2(df=1)=9.43; genetic variation in SLC1A3 may contribute to susceptibility to ADHD More... | Significant |
Copyright: Bioinformatics Lab, Institute of Psychology, Chinese Academy of Sciences Feedback
Last update: Feb 26, 2014



