Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder.

TitleGenome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder.
Publication TypeJournal Article
Year of Publication2008
AuthorsMick, E, Neale B, Middleton FA, McGough JJ, Faraone SV
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Date Published2008 Dec 5
KeywordsAttention Deficit Disorder with Hyperactivity, Central Nervous System Stimulants, Chi-Square Distribution, Child, Clinical Trials, Phase IV as Topic, DNA, Dose-Response Relationship, Drug, Female, Genetic Markers, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Male, Methylphenidate, Multicenter Studies as Topic, Norepinephrine Plasma Membrane Transport Proteins, Nucleic Acid Amplification Techniques, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Probability, Receptors, Metabotropic Glutamate

We conducted a genome-wide association study of symptom response in an open-label study of a methylphenidate transdermal system (MTS). All DNA extraction and genotyping was conducted at SUNY Upstate Medical University using the Affymetrix Genome-Wide Human SNP Array 6.0. All quality control and association analyses were conducted using the software package PLINK. After data cleaning and quality control, there were 187 subjects (72% (N = 135) male) with mean age 9.2 +/- 2.0 years and 319,722 SNPs available for analysis. The most statistically significant association (rs9627183 and rs11134178; P = 3 x 10(-6)) fell short of the threshold for a genome-wide significant association. The most intriguing association among suggestive findings (rs3792452; P = 2.6 x 10(-5)) was with the metabotropic glutamate receptor 7 gene (GRM7) as it is expressed in brain structures also previously associated with ADHD. Among the 102 available SNPs covering previously studied candidate genes, two SNPs within the norepinephrine transporter gene (NET, SLC6A2) were significant at P < or = 1 x 10(-2). These results should be considered preliminary until replicated in larger adequately powered, controlled samples but do suggest that noradrenergic and possibly glutaminergic genes may be involved with response to methylphenidate.

Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.