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

Stefan Johansson, Anne Halmøy, Thegna Mavroconstanti, Kaya K. Jacobsen, Elisabeth T. Landaas, Andreas Reif, Christian Jacob, Andrea Boreatti-Hümmer, Susanne Kreiker, Klaus-Peter Lesch, Cornelis C. Kan, J. J. Sandra Kooij, Lambertus A. Kiemeney, Jan K. Buitelaar, Barbara Franke, Marta Ribasés, Rosa Bosch, M. nica Bayés, Miguel Casas, Josep Antoni Ramos-Quiroga & 3 others Bru Cormand, Per Knappskog, Jan Haavik

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)1008-1015
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

Cite this

Johansson, Stefan ; Halmøy, Anne ; Mavroconstanti, Thegna ; Jacobsen, Kaya K. ; Landaas, Elisabeth T. ; Reif, Andreas ; Jacob, Christian ; Boreatti-Hümmer, Andrea ; Kreiker, Susanne ; Lesch, Klaus-Peter ; Kan, Cornelis C. ; Kooij, J. J. Sandra ; Kiemeney, Lambertus A. ; Buitelaar, Jan K. ; Franke, Barbara ; Ribasés, Marta ; Bosch, Rosa ; Bayés, M. nica ; Casas, Miguel ; Ramos-Quiroga, Josep Antoni ; Cormand, Bru ; Knappskog, Per ; Haavik, Jan. / 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. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2010 ; Vol. 153, No. 5. pp. 1008-1015.
@article{e08069089cd545a09c1778d7880c7564,
title = "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",
abstract = "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. {\circledC} 2010 Wiley-Liss, Inc.",
author = "Stefan Johansson and Anne Halm{\o}y and Thegna Mavroconstanti and Jacobsen, {Kaya K.} and Landaas, {Elisabeth T.} and Andreas Reif and Christian Jacob and Andrea Boreatti-H{\"u}mmer and Susanne Kreiker and Klaus-Peter Lesch and Kan, {Cornelis C.} and Kooij, {J. J. Sandra} and Kiemeney, {Lambertus A.} and Buitelaar, {Jan K.} and Barbara Franke and Marta Ribas{\'e}s and Rosa Bosch and Bay{\'e}s, {M. nica} and Miguel Casas and Ramos-Quiroga, {Josep Antoni} and Bru Cormand and Per Knappskog and Jan Haavik",
year = "2010",
doi = "10.1002/ajmg.b.31067",
language = "English",
volume = "153",
pages = "1008--1015",
journal = "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "5",

}

Johansson, S, Halmøy, A, Mavroconstanti, T, Jacobsen, KK, Landaas, ET, Reif, A, Jacob, C, Boreatti-Hümmer, A, Kreiker, S, Lesch, K-P, Kan, CC, Kooij, JJS, Kiemeney, LA, Buitelaar, JK, Franke, B, Ribasés, M, Bosch, R, Bayés, MN, Casas, M, Ramos-Quiroga, JA, Cormand, B, Knappskog, P & Haavik, J 2010, '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' American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 153, no. 5, pp. 1008-1015. https://doi.org/10.1002/ajmg.b.31067

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. / Johansson, Stefan; Halmøy, Anne; Mavroconstanti, Thegna; Jacobsen, Kaya K.; Landaas, Elisabeth T.; Reif, Andreas; Jacob, Christian; Boreatti-Hümmer, Andrea; Kreiker, Susanne; Lesch, Klaus-Peter; Kan, Cornelis C.; Kooij, J. J. Sandra; Kiemeney, Lambertus A.; Buitelaar, Jan K.; Franke, Barbara; Ribasés, Marta; Bosch, Rosa; Bayés, M. nica; Casas, Miguel; Ramos-Quiroga, Josep Antoni; Cormand, Bru; Knappskog, Per; Haavik, Jan.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 153, No. 5, 2010, p. 1008-1015.

Research output: Contribution to journalArticleAcademicpeer-review

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, M. nica

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. © 2010 Wiley-Liss, Inc.

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. © 2010 Wiley-Liss, Inc.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77954357411&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/20213726

U2 - 10.1002/ajmg.b.31067

DO - 10.1002/ajmg.b.31067

M3 - Article

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

SN - 1552-4841

IS - 5

ER -