ANRIL Variants Are Associated with Risk of Neuropsychiatric Conditions

The antisense non-coding RNA in the INK4 locus (ANRIL) is a long non-coding RNA (lncRNA) whose contribution in several human disorders has been verified. In the current projects, we genotyped two single nucleotide polymorphisms (SNPs) in this lncRNA (rs1333045 and rs1333048) in a population of Iranian patients with bipolar disorder (BP), major depressive disorder (MDD), and methamphetamine addiction. The rs1333045 was associated with methamphetamine addiction in recessive and multiplicative models (OR (95% CI) = 1.867 (1.211-2.877), adjusted p value = 8.75E-03 and OR (95% CI) = 1.415 (1.089-1.839), adjusted p value = 1.87E-02 respectively). The rs1333048 was associated with methamphetamine addiction in co-dominant model (A/A vs. C/C: OR (95% CI) = 0.195 (0.114-0.336), adjusted p value = 2.44E-09) and in other inheritance models. The rs1333045 was not associated with risk of BP I in any inheritance model. However, the rs1333048 was associated with BP I in co-dominant model (A/A vs. C/C: OR (95% CI) = 0.499 (0.286-0.870), adjusted p value = 2.53E-07) and in other inheritance models. In BP II cohort, we detected significant associations between both SNPs and risk of disorder in all inheritance models. In co-dominant model, these associations were detected just between homozygotes (T/T vs. C/C (rs1333045); A/A vs. C/C and (rs1333048)). The rs1333045 was associated with MDD in recessive model (OR (95% CI) = 2.221 (1.173-4.207), adjusted p value = 0.026). The rs1333048 was associated with MDDs in dominant, recessive, and multiplicative models. The selected SNPs were not in linkage disequilibrium (D' statistic = 0.23, r² = 0.05). Haplotype analyses have shown that T A haplotype block (rs1333045 and rs1333048 respectively) significantly decreases risk of addiction, BP I, BP II, and MDD. Besides, the C C haplotype decreases risk of addiction, BP II and MDD. Finally, the T C haplotype increases risk of BP I, BP II, and MDD. Based on the above-mentioned data, the selected ANRIL SNPs or other SNPs in linkage disequilibrium with them might confer risk of neuropsychiatric disorders. Taken together, ANRIL can be regarded as a risk locus for these conditions.