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). METHOD: 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.
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). METHOD: 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.
Authors: Andreas Windemuth; Jose de Leon; John W Goethe; Harold I Schwartz; Stephen Woolley; Margaret Susce; Mohan Kocherla; Kali Bogaard; Theodore R Holford; Richard L Seip; Gualberto Ruaño Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2011-08-06 Impact factor: 5.067
Authors: Kevin M Antshel; Teresa M Hargrave; Mihai Simonescu; Prashant Kaul; Kaitlin Hendricks; Stephen V Faraone Journal: BMC Med Date: 2011-06-10 Impact factor: 8.775
Authors: Dorothee Busold-Hagenbeck; Julia Elmenhorst; Christoph Irtel von Brenndorff; Reinhard Hilgers; Martin Hulpke-Wette Journal: Gen Psychiatr Date: 2020-04-26