An international multicenter association study of the serotonin transporter gene in persistent ADHD

E. T. Landaas, S. Johansson, K. K. Jacobsen, M. Ribasés, R. Bosch, C. Sánchez-Mora, C. P. Jacob, A. Boreatti-Hümmer, S. Kreiker, K. P. Lesch, L. A. Kiemeney, J. J. S. Kooij, C. Kan, J. K. Buitelaar, S. V. Faraone, A. Halmøy, J. A. Ramos-Quiroga, B. Cormand, A. Reif, B. Franke & 3 others E. Mick, P. M. Knappskog, J. Haavik

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded. © 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.
Original languageEnglish
Pages (from-to)449-458
JournalGenes, brain, and behavior
Volume9
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

Cite this

Landaas, E. T., Johansson, S., Jacobsen, K. K., Ribasés, M., Bosch, R., Sánchez-Mora, C., ... Haavik, J. (2010). An international multicenter association study of the serotonin transporter gene in persistent ADHD. Genes, brain, and behavior, 9(5), 449-458. https://doi.org/10.1111/j.1601-183X.2010.00567.x
Landaas, E. T. ; Johansson, S. ; Jacobsen, K. K. ; Ribasés, M. ; Bosch, R. ; Sánchez-Mora, C. ; Jacob, C. P. ; Boreatti-Hümmer, A. ; Kreiker, S. ; Lesch, K. P. ; Kiemeney, L. A. ; Kooij, J. J. S. ; Kan, C. ; Buitelaar, J. K. ; Faraone, S. V. ; Halmøy, A. ; Ramos-Quiroga, J. A. ; Cormand, B. ; Reif, A. ; Franke, B. ; Mick, E. ; Knappskog, P. M. ; Haavik, J. / An international multicenter association study of the serotonin transporter gene in persistent ADHD. In: Genes, brain, and behavior. 2010 ; Vol. 9, No. 5. pp. 449-458.
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abstract = "Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95{\%} confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95{\%} CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded. {\circledC} 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.",
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Landaas, ET, Johansson, S, Jacobsen, KK, Ribasés, M, Bosch, R, Sánchez-Mora, C, Jacob, CP, Boreatti-Hümmer, A, Kreiker, S, Lesch, KP, Kiemeney, LA, Kooij, JJS, Kan, C, Buitelaar, JK, Faraone, SV, Halmøy, A, Ramos-Quiroga, JA, Cormand, B, Reif, A, Franke, B, Mick, E, Knappskog, PM & Haavik, J 2010, 'An international multicenter association study of the serotonin transporter gene in persistent ADHD' Genes, brain, and behavior, vol. 9, no. 5, pp. 449-458. https://doi.org/10.1111/j.1601-183X.2010.00567.x

An international multicenter association study of the serotonin transporter gene in persistent ADHD. / Landaas, E. T.; Johansson, S.; Jacobsen, K. K.; Ribasés, M.; Bosch, R.; Sánchez-Mora, C.; Jacob, C. P.; Boreatti-Hümmer, A.; Kreiker, S.; Lesch, K. P.; Kiemeney, L. A.; Kooij, J. J. S.; Kan, C.; Buitelaar, J. K.; Faraone, S. V.; Halmøy, A.; Ramos-Quiroga, J. A.; Cormand, B.; Reif, A.; Franke, B.; Mick, E.; Knappskog, P. M.; Haavik, J.

In: Genes, brain, and behavior, Vol. 9, No. 5, 2010, p. 449-458.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - An international multicenter association study of the serotonin transporter gene in persistent ADHD

AU - Landaas, E. T.

AU - Johansson, S.

AU - Jacobsen, K. K.

AU - Ribasés, M.

AU - Bosch, R.

AU - Sánchez-Mora, C.

AU - Jacob, C. P.

AU - Boreatti-Hümmer, A.

AU - Kreiker, S.

AU - Lesch, K. P.

AU - Kiemeney, L. A.

AU - Kooij, J. J. S.

AU - Kan, C.

AU - Buitelaar, J. K.

AU - Faraone, S. V.

AU - Halmøy, A.

AU - Ramos-Quiroga, J. A.

AU - Cormand, B.

AU - Reif, A.

AU - Franke, B.

AU - Mick, E.

AU - Knappskog, P. M.

AU - Haavik, J.

PY - 2010

Y1 - 2010

N2 - Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded. © 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.

AB - Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting children and adults. It has been suggested that gene variants related to serotonin neurotransmission are associated with ADHD. We tested the functional promoter polymorphism 5-HTTLPR and seven single nucleotide polymorphisms in SLC6A4 for association with ADHD in 448 adult ADHD patients and 580 controls from Norway. Replication attempts were performed in a sample of 1454 Caucasian adult ADHD patients and 1302 controls from Germany, Spain, the Netherlands and USA, and a meta-analysis was performed also including a previously published adult ADHD study. We found an association between ADHD and rs140700 [odds ratio (OR) = 0.67; P = 0.01] and the short (S) allele of the 5-HTTLPR (OR = 1.19; P = 0.06) in the Norwegian sample. Analysis of a possible gender effect suggested that the association might be restricted to females (rs140700: OR = 0.45; P = 0.00084). However, the meta-analysis of 1894 cases and 1878 controls could not confirm the association for rs140700 [OR = 0.85, 95% confidence interval (CI) = 0.67-1.09; P = 0.20]. For 5-HTTLPR, five of six samples showed a slight overrepresentation of the S allele in patients, but meta-analysis refuted a strong effect (OR = 1.10, 95% CI = 1.00-1.21; P = 0.06). Neither marker showed any evidence of differential effects for ADHD subtype, gender or symptoms of depression/anxiety. In conclusion, our results do not support a major role for SLC6A4 common variants in persistent ADHD, although a modest effect of the 5-HTTLPR and a role for rare variants cannot be excluded. © 2010 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society.

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