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Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder.
- Source :
-
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] 2008 Dec 05; Vol. 147B (8), pp. 1412-8. - Publication Year :
- 2008
-
Abstract
- 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.<br /> (Copyright 2008 Wiley-Liss, Inc.)
- Subjects :
- Attention Deficit Disorder with Hyperactivity diagnosis
Central Nervous System Stimulants adverse effects
Chi-Square Distribution
Child
Clinical Trials, Phase IV as Topic
DNA blood
DNA genetics
DNA metabolism
Dose-Response Relationship, Drug
Female
Genetic Markers
Genome, Human
Genotype
Humans
Male
Methylphenidate adverse effects
Multicenter Studies as Topic
Norepinephrine Plasma Membrane Transport Proteins genetics
Nucleic Acid Amplification Techniques
Oligonucleotide Array Sequence Analysis
Polymorphism, Single Nucleotide
Probability
Receptors, Metabotropic Glutamate genetics
Attention Deficit Disorder with Hyperactivity genetics
Central Nervous System Stimulants pharmacology
Genome-Wide Association Study
Methylphenidate pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1552-485X
- Volume :
- 147B
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 18821564
- Full Text :
- https://doi.org/10.1002/ajmg.b.30865