Genome‐wide association study of response to methylphenidate in 187 children with attention‐deficit/hyperactivity disorder
Open accessAbstract
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 × 10−6) fell short of the threshold for a genome‐wide significant association. The most intriguing association among suggestive findings (rs3792452; P = 2.6 × 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 ≤ 1 × 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. © 2008 Wiley‐Liss, Inc.
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Pharmacogenetic research on ADHD treatment, although promising, cannot yet guide treatment choices.
“which, although promising, cannot yet guide treatment choices [132-134]”
From Advances in understanding and treating ADHD (2011) · cites this paper as [134]
To date, most work on using neurobiology to tailor ADHD treatment has been done in pharmacogenetics.
“To date, most of this work has been done in the area of pharmacogenetics”
From Advances in understanding and treating ADHD (2011) · cites this paper as [134]
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- Authors
- Mick, E., Neale, B., Middleton, F. A., McGough, J. J., & Faraone, S. V.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- SUNY Upstate Medical University (US)
- University of California, Los Angeles (US)
- Corresponding author
- Mick, Eric
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2008-09-26
- Volume
- 147B
- Issue
- 8
- Pages
- 1412-1418
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2056095008
- Cited by
- 108
- References
- 39
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 10 · 2013: 7 · 2012: 9
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- SUNY Digital Repository Support (State University of New York System) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (U01MH085518)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, methylphenidate response, pharmacogenetics, single nucleotide polymorphisms, GRM7, mGluR7, norepinephrine transporter, children
- MeSH terms
- Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, DNA, Dose-Response Relationship, Drug, Female, Genetic Markers, Genotype, Humans, Male, Methylphenidate, Probability, Multicenter Studies as Topic, Genome, Human, Chi-Square Distribution, Clinical Trials, Phase IV as Topic, Receptors, Metabotropic Glutamate, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Nucleic Acid Amplification Techniques, Norepinephrine Plasma Membrane Transport Proteins, Genome-Wide Association Study
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