Study Report

Basic Info
Reference |
Brookes KJ, 2006(a)16893529
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Citation |
Brookes K. J., Chen W., Xu X., Taylor E. and Asherson P. (2006) "Association of fatty acid desaturase genes with attention-deficit/hyperactivity disorder." Biol Psychiatry, 60(10): 1053-61.
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Study Design |
case-control and family-based |
Study Type |
Candidate-gene association study |
Sample Size |
180 individual probands, 90 unrelated female and 90 unrelated male controls |
Predominant Ethnicity |
Caucasian |
Population |
United Kingdom |
Gender |
96% male probands, 90 unrelated female and 90 unrelated male controls |
Age Group |
Children/Adolescents
:
5-15 years
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Detail Info
Summary |
They investigated three genes that encode essential enzymes (desaturases) for the metabolism of fatty acids by scanning for genetic association between 45 single nucleotide polymorphisms (SNPs) and ADHD. Their findings suggest a significant association of ADHD with SNP rs498793 in the fatty acid desaturase 2 (FADS2) gene. As alcohol is known to decrease the activities of these desaturase enzymes, they also tested for interactions between ADHD subjects' genotypes and maternal use of alcohol during pregnancy. Two SNPs in the fatty acid desaturase 1 (FADS1) gene were nominally associated with ADHD only in the prenatal alcohol-exposed group of children; formal test for interaction was not significant. |
Total Sample |
The sample analyzed here consists of 180 individual probands. DNA was available from both parents for 116 probands and from the mother alone for 64 probands. Ninety-six percent of the sample was male subjects. The age range was 5 to 15 years at the time of assessment (mean=10.41, SD=2.34). The control sample was generated from ethnically matched individuals taking part in a population twin sample. This comprised 90 unrelated female and 90 unrelated male individuals with low scores (bottom 20% of distribution) on a composite index of ADHD symptom scores. |
Sample Collection |
Caucasian ethnicity |
Diagnosis Description |
Cases were referred for assessment if they were thought by experienced clinicians to have a diagnosis of the combined subtype of ADHD under DSM-IV criteria with no significant Axis I comorbidity apart from oppositional defiant disorder (ODD) and conduct disorder (CD). Parents of referred cases were interviewed with a modified version of the Child and Adolescent Psychiatric Assessment (CAPA). Information on ADHD symptoms at school was obtained using the long form of the Conners Rating Scale. All probands had a research diagnosis of ADHD combined subtype following the DSM-IV criteria. |
Technique |
Polymerase chain reaction (PCR) products spanning each SNP marker were amplified using a standard PCR protocol: initial 5 minutes denaturing step at 95oC, followed by 30 cycles of 95oC for 1 minute, 55oC for 1 minute, and 72oC for 1 minute, and a final extension step of 72oC for 10 minutes. Primers were designed for each SNP using Primer 3 software (Whitehead Institute for Biomedical Research; Rozen and Skatetsky 2000) (http://www. genome.wi.mit.edu/cgi-bin/primer/primer3.cgi/primer3_www. cgi) from the sequence data on the Single Nucleotide Polymorphism database (dbSNP) (http://www.ncbi.nlm.nih.gov/SNP/). |
Analysis Method |
If a marker obtained a P-value <0.1 from the MRM, the marker was individually genotyped. All the individual samples from the four pools were genotyped, plus the parents of the probands. These data were used to generate the true case-control differences and perform within-family tests of association using the transmission disequilibrium test (TDT) implemented using the UNPHASED program (www.rfcgr.mrc.ac.United Kingdom/ fdudbrid/ software/unphased). |
Result Description |
Their findings suggest a significant association of ADHD with SNP rs498793 (case-control P-value=0.004, odds ratio [OR] 1.6, 95% confidence interval [CI] 1.15-2.23; transmission disequilibrium test [TDT] P-value=0.014, OR 1.9) in the fatty acid desaturase 2 (FADS2) gene. The preliminary findings are suggestive of an association between FADS2 and ADHD. |

SNPs reported by this study (count: 3)
SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
rs498793 |
C/T |
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allelic P-value=0.0037, OR=1.6; TDT P-value=0.013, OR=1.69 (C allele), OR=0.53 (T allele); HHRR P-value=0.018, OR=1.2 (C allele), OR=0.75 (T allele) |
significant association with ADHD was detected in both case-......
significant association with ADHD was detected in both case-control and within-family analyses
More...
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Significant
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rs174548 |
C/G |
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allelic P-value=0.9, OR=1.02; TDT P-value=0.191, OR=0.73 (C allele), OR=1.37 (G allele); HHRR P-value=0.24, OR=0.94 (C allele), OR=1.21 (G allele) |
was not statistically significant
was not statistically significant
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Non-significant
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rs174545 |
C/G |
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allelic P-value=0.59, OR=0.91; TDT P-value=0.262, OR=0.78 (C allele), OR=1.29 (G allele); HHRR P-value=0.31, OR=0.94 (C allele), OR=1.16 (G allele) |
was not statistically significant
was not statistically significant
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Non-significant
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Genes reported by this study (count: 2)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
FADS1 |
no evidence from case-control or within family tests of asso......
no evidence from case-control or within family tests of association for a haplotype specific association with the two SNPs in FADS1
More...
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Non-significant
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FADS2 |
1 SNP showed significant association in both case-control an......
1 SNP showed significant association in both case-control and within-family analyses, which are suggestive of an association between FADS2 and ADHD
More...
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Significant
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