TY - JOUR
T1 - Common variants in the TPH1 and TPH2 regions are not associated with persistent ADHD in a combined sample of 1,636 adult cases and 1,923 controls from four European populations
AU - Johansson, Stefan
AU - Halmøy, Anne
AU - Mavroconstanti, Thegna
AU - Jacobsen, Kaya K.
AU - Landaas, Elisabeth T.
AU - Reif, Andreas
AU - Jacob, Christian
AU - Boreatti-Hümmer, Andrea
AU - Kreiker, Susanne
AU - Lesch, Klaus Peter
AU - Kan, Cornelis C.
AU - Kooij, J. J.Sandra
AU - Kiemeney, Lambertus A.
AU - Buitelaar, Jan K.
AU - Franke, Barbara
AU - Ribasés, Marta
AU - Bosch, Rosa
AU - Bayés, Mònica
AU - Casas, Miguel
AU - Ramos-Quiroga, Josep Antoni
AU - Cormand, Bru
AU - Knappskog, Per
AU - Haavik, Jan
PY - 2010
Y1 - 2010
N2 - The tryptophan hydroxylase 1 and 2 (TPH1 and TPH2) genes encode the rate-limiting enzymes in the serotonin biosynthesis. Genetic variants in both genes have been implicated in several psychiatric disorders. For attention-deficit/hyperactivity disorder (ADHD) in children, the results are conflicting, and little is known about their role in adult ADHD patients. We therefore first genotype-tagged all common variants within both genes in a Norwegian sample of 451 patients with a diagnosis of adult ADHD and 584 controls. Six of the single nucleotide polymorphisms (SNPs) were subsequently genotyped in three additional independent European Caucasian samples of adult ADHD cases and controls from the International Multicenter persistent ADHD Collaboration (IMpACT). None of the SNPs reached formal study-wide significance in the total meta-analysis sample of 1,636 cases and 1,923 controls, despite having a power of >80% to detect a variant conferring an OR = 1.25 at P = 0.001 level. Only the TPH1 SNP rs17794760 showed nominal significance [OR = 0.84 (0.71-1.00), P = 0.05]. In conclusion, in the single largest ADHD genetic study of TPH1 and TPH2 variants presented to date (n = 3,559 individuals), we did not find consistent evidence for a substantial effect of common genetic variants on persistent ADHD.
AB - The tryptophan hydroxylase 1 and 2 (TPH1 and TPH2) genes encode the rate-limiting enzymes in the serotonin biosynthesis. Genetic variants in both genes have been implicated in several psychiatric disorders. For attention-deficit/hyperactivity disorder (ADHD) in children, the results are conflicting, and little is known about their role in adult ADHD patients. We therefore first genotype-tagged all common variants within both genes in a Norwegian sample of 451 patients with a diagnosis of adult ADHD and 584 controls. Six of the single nucleotide polymorphisms (SNPs) were subsequently genotyped in three additional independent European Caucasian samples of adult ADHD cases and controls from the International Multicenter persistent ADHD Collaboration (IMpACT). None of the SNPs reached formal study-wide significance in the total meta-analysis sample of 1,636 cases and 1,923 controls, despite having a power of >80% to detect a variant conferring an OR = 1.25 at P = 0.001 level. Only the TPH1 SNP rs17794760 showed nominal significance [OR = 0.84 (0.71-1.00), P = 0.05]. In conclusion, in the single largest ADHD genetic study of TPH1 and TPH2 variants presented to date (n = 3,559 individuals), we did not find consistent evidence for a substantial effect of common genetic variants on persistent ADHD.
KW - ADHD
KW - Common variants
KW - Genetic analysis
KW - TPH1
KW - TPH2
UR - http://www.scopus.com/inward/record.url?scp=77954357411&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.31067
DO - 10.1002/ajmg.b.31067
M3 - Article
C2 - 20213726
AN - SCOPUS:77954357411
SN - 1552-4841
VL - 153
SP - 1008
EP - 1015
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 5
ER -
