Replication test for association of the IL-1 receptor antagonist gene, IL1RN, with attention-deficit/hyperactivity...

Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and aberrant brain dopaminergic and noradrenergic activity is implicated in its etiology. Interleukin-1 (IL-1), its antagonist, IL-1Ra, and IL-1 receptors are all present in the brain, and IL-1 has been shown to influence both dopaminergic and noradrenergic function. Recently, Segman et al. [1] tested the IL-1Ra gene, IL1RN, as a candidate for involvement in ADHD. Using the transmission/disequilibrium test (TDT) to examine 77 nuclear ADHD families for the inheritance of alleles of an intronic 86-bp VNTR polymorphism, they found significant evidence for biased transmission of the 4-repeat allele (p=0.04) and non-transmission of the 2-repeat allele (p=0.03). Here, we sought to replicate this in an independent sample of families. In contrast to the previous findings, our analysis of 178 ADHD families showed no evidence for biased transmission of these alleles (p=0.81 and p=1.00, respectively). Our lack of evidence for association of this IL1RN polymorphism with ADHD, based on a much larger sample of families, suggests that the original finding may have been a spurious (i.e. false-positive) result. These findings highlight the need for further investigations of this marker, in additional independent ADHD samples, in the future.