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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
Author(s) -
Johansson Stefan,
Halmøy Anne,
Mavroconstanti Thegna,
Jacobsen Kaya K.,
Landaas Elisabeth T.,
Reif Andreas,
Jacob Christian,
BoreattiHümmer Andrea,
Kreiker Susanne,
Lesch KlausPeter,
Kan Cornelis C.,
Kooij J.J. Sandra,
Kiemeney Lambertus A.,
Buitelaar Jan K.,
Franke Barbara,
Ribasés Marta,
Bosch Rosa,
Bayés Mònica,
Casas Miguel,
RamosQuiroga Josep Antoni,
Cormand Bru,
Knappskog Per,
Haavik Jan
Publication year - 2010
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31067
Subject(s) - tph2 , single nucleotide polymorphism , attention deficit hyperactivity disorder , genetics , norwegian , snp , tryptophan hydroxylase , biology , gene , genotype , medicine , psychiatry , serotonin , linguistics , philosophy , receptor , serotonergic
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. © 2010 Wiley‐Liss, Inc.