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.
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.
Johansson
Stefan
S
Department of Biomedicine, University of Bergen, Bergen, Norway. stefan.johansson@biomed.uib.no
Halmøy
Anne
A
Mavroconstanti
Thegna
T
Jacobsen
Kaya K
KK
Landaas
Elisabeth T
ET
Reif
Andreas
A
Jacob
Christian
C
Boreatti-Hümmer
Andrea
A
Kreiker
Susanne
S
Lesch
Klaus-Peter
KP
Kan
Cornelis C
CC
Kooij
J J Sandra
JJ
Kiemeney
Lambertus A
LA
Buitelaar
Jan K
JK
Franke
Barbara
B
Ribasés
Marta
M
Bosch
Rosa
R
Bayés
Mònica
M
Casas
Miguel
M
Ramos-Quiroga
Josep Antoni
JA
Cormand
Bru
B
Knappskog
Per
P
Haavik
Jan
J
D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D005091:Exons / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D009664:Norway; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D044465:White People / Q000235:genetics*
D005819:Genetic Markers; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase