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Replication of a rare protective allele in the noradrenaline transporter gene and ADHD


Xu, X; Hawi, Z; Brookes, K J; Anney, R; Bellgrove, M; Franke, B; Barry, E; Chen, W; Kuntsi, J; Banaschewski, T; Buitelaar, J; Ebstein, R; Fitzgerald, M; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Sonuga-Barke, E; Steinhausen, H C; Faraone, S V; Gill, M; Asherson, P (2008). Replication of a rare protective allele in the noradrenaline transporter gene and ADHD. American Journal of Medical Genetics. Part B, 147B(8):1564-1567.

Abstract

Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P = 0.0001; average odds ratio = 0.33; for SNP rs3785143 P = 0.008; average odds ratio = 1.3). The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect. (c) 2008 Wiley-Liss, Inc.

Abstract

Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P = 0.0001; average odds ratio = 0.33; for SNP rs3785143 P = 0.008; average odds ratio = 1.3). The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect. (c) 2008 Wiley-Liss, Inc.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:5 December 2008
Deposited On:12 Dec 2008 11:12
Last Modified:21 Nov 2017 13:40
Publisher:Wiley-Blackwell
ISSN:1552-4841
Publisher DOI:https://doi.org/10.1002/ajmg.b.30872
PubMed ID:18937296

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