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	Brookes KJ, 2006(a)16893529
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.
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

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 95^oC, followed by 30 cycles of 95^oC for 1 minute, 55^oC for 1 minute, and 72^oC for 1 minute, and a final extension step of 72^oC 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		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...	Significant
rs174545	C/G		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	Non-significant
rs174548	C/G		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	Non-significant

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...	Non-significant
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...	Significant