Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder.
OBJECTIVE
We conducted a genome-wide association study of blood pressure in an open-label study of the methylphenidate transdermal system (MTS) for the treatment of attention-deficit/hyperactivity disorder (ADHD).


METHODS
Genotyping was conducted with the Affymetrix Genome-Wide Human SNP Array 6.0. Multivariate association analyses were conducted using the software package PLINK. After data cleaning and quality control we tested 316,934 SNPs in 140 children with ADHD.


RESULTS
We observed no genome-wide statistically significant findings, but a SNP in a K(+)-dependent Na(+)/Ca(2+) exchanger expressed in vascular smooth muscle (SLC24A3) was included in our top associations at p<1E-04. Genetic enrichment analyses of genes with ≥1 SNP significant at p<0.01, implicated several functional categories (FERM domain, p=5.0E-07; immunoglobulin domain, p=8.1E-06; the transmembrane region, p=4.4E-05; channel activity, p=2.0E-04; and type-III fibronectins, p=2.7E-05) harboring genes previously associated with related cardiovascular phenotypes.


CONCLUSIONS
The hypothesis generating results from this study suggests that polymorphisms in several genes consistently associated with cardiovascular diseases may impact changes in blood pressure observed with methylphenidate pharmacotherapy in children with ADHD.
Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States. mick@helix.mgh.harvard.edu
Eric
E
Mick
James J
JJ
McGough
Frank A
FA
Middleton
Benjamin
B
Neale
Stephen V
SV
Faraone
D000279:Administration, Cutaneous; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000235:genetics; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
D000697:Central Nervous System Stimulants; C430914:SLC24A3 protein, human; D019831:Sodium-Calcium Exchanger; D008774:Methylphenidate