Differential dopamine receptor D4 allele association with ADHD dependent on proband season of birth

Brookes, Keeley Joane; Neale, Benjamin M.; Xu, Xiaohui; Thapar, Anita; Gill, Michael; Langley, Kate; Hawi, Ziarih; Miller, Jörg LSF; Taylor, Eric A; Franke, Barbara; Chen, Wai; Ebstein, Richard; Buitelaar, Jan K; Banaschewski, Tobias; Sonuga-Barke, Edmund J.S.; Eisenberg, Jacques; Manor, Iris; Miranda, Ana; Oades, Robert D. LSF; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Asherson, Philip

Season of birth (SOB) has been associated with attention deficit hyperactivity disorder (ADHD) in two existing studies. One further study reported an interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It is important that these findings are further investigated to confirm or refute the findings. In this study, we investigated the SOB association with ADHD in four independent samples collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. We also observed a significant association with the 7-repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this allele between summer and winter seasons. Preferential transmission of the 2-repeat allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of alleles none of the SOB effects remained significant. We conclude that the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD. Our findings suggest that we can refute a possible effect of SOB for ADHD.


Citation style:
Brookes, K.J., Neale, B.M., Xu, X., Thapar, A., Gill, M., Langley, K., Hawi, Z., Miller, J., Taylor, E.A., Franke, B., Chen, W., Ebstein, R., Buitelaar, J.K., Banaschewski, T., Sonuga-Barke, E.J.S., Eisenberg, J., Manor, I., Miranda, A., Oades, R.D., Roeyers, H., Rothenberger, A., Sergeant, J.A., Steinhausen, H.-C., Faraone, S.V., Asherson, P., 2011. Differential dopamine receptor D4 allele association with ADHD dependent on proband season of birth. https://doi.org/10.1002/ajmg.b.30562
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