Association of Fatty Acid Desaturase Genes with Attention-Deficit/Hyperactivity Disorder

• Published in: Biological psychiatry (1969) 2006-11, Vol.60 (10), p.1053-1061
• Main Authors: Brookes, Keeley J., Chen, Wai, Xu, Xiaohui, Taylor, Eric, Asherson, Philip
• Format: Article
• Language: English
• Subjects: Adolescent; Alcohols - adverse effects; Attention Deficit Disorder with Hyperactivity - blood; Attention Deficit Disorder with Hyperactivity - etiology; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit disorders. Hyperactivity; Attention-deficit/hyperactivity disorder (ADHD); Biological and medical sciences; Case-Control Studies; Child; Child clinical studies; Confidence Intervals; DNA pooling; fatty acid desaturase (FADS) genes; Fatty Acid Desaturases - blood; Fatty Acid Desaturases - genetics; fatty acids; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Linkage Disequilibrium; Male; Maternal Exposure - adverse effects; Medical sciences; Odds Ratio; omega-3; Polymorphism, Single Nucleotide; Pregnancy; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk Factors
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.04.025

Fatty acids, in particular omega-3 fatty acids, have been found to affect behavior and cognition both directly and indirectly. Evidence to suggest a link with attention-deficit/hyperactivity disorder (ADHD) derives from three key areas: 1) animal dietary restriction studies observed increased locomotive hyperactivity and reduced cognitive ability in offspring; 2) animal dietary studies indicate alterations in the dopamine pathway; and 3) human studies report reduced plasma omega-3 fatty acids in ADHD subjects. We 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. Our findings suggest a significant association of ADHD with SNP rs498793 (case-control p = .004, odds ratio [OR] 1.6, 95% confidence interval [CI] 1.15–2.23; transmission disequilibrium test [TDT] p = .014, OR 1.69) in the fatty acid desaturase 2 (FADS2) gene. As alcohol is known to decrease the activities of these desaturase enzymes, we 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. These preliminary findings are suggestive of an association between FADS2 and ADHD.