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Xu, X., Hawi, Z., Brookes, K-J., Anney, R. J.
L., Bellgrove, M. A., Franke, B., Barry, E., Chen, W., Kuntsi, J., Banaschewski,
T., Buitelaar, J. K., Ebstein, R. P., Fitzgerald, M., Miranda, A., Oades,
R. D., Roeyers, H., Rothenberger, A., Sergeant, J. A., Sonuga-Barke,
E. J. S., Steinhausen, H-C., Faraone, S.V., Gill, M. & Asherson,
P.. Introduction: 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), 2 SNPs within the NA transporter (SLC6A2 = NET1) gene were found to be associated with ADHD . The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the USA. Methods: Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 & rs3785143 in SLC6A2. Results: 2 - However, across all 4 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). Discussion: 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. |