ANRIL Variants Are Associated with Risk of Neuropsychiatric Conditions

Background and Aim: The antisense non-coding RNA in the INK۴ locus (ANRIL) is a long non-coding RNA (lncRNA) whose contribution in several human disorders has been verified.Methods: In the current projects, we genotyped two single nucleotide polymorphisms (SNPs) in this lncRNA (rs۱۳۳۳۰۴۵ and rs۱۳۳۳۰۴۸) in a population of Iranian patients with bipolar disorder (BP), major depressive disorder (MDD), and methamphetamine addiction.Results: The rs۱۳۳۳۰۴۵ was associated with methamphetamine addiction in recessive and multiplicative models (OR (۹۵% CI) = ۱.۸۶۷ (۱.۲۱۱–۲.۸۷۷), adjusted p value = ۸.۷۵E−۰۳ and OR(۹۵% CI) = ۱.۴۱۵ (۱.۰۸۹– ۱.۸۳۹), adjusted p value = ۱.۸۷E−۰۲ respectively). The rs۱۳۳۳۰۴۸ was associated with methamphetamine addiction in codominant model (A/A vs. C/C: OR (۹۵% CI) = ۰.۱۹۵ (۰.۱۱۴–۰.۳۳۶), adjusted p value = ۲.۴۴E−۰۹) and in other inheritance models. The rs۱۳۳۳۰۴۵ was not associated with risk of BP I in any inheritance model. However, the rs۱۳۳۳۰۴۸ was associated with BP I in co-dominant model (A/A vs. C/C: OR (۹۵% CI) = ۰.۴۹۹ (۰.۲۸۶–۰.۸۷۰), adjusted p value = ۲.۵۳E−۰۷) 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 (rs۱۳۳۳۰۴۵); A/A vs. C/C and (rs۱۳۳۳۰۴۸)). The rs۱۳۳۳۰۴۵ was associated with MDD in recessive model (OR (۹۵% CI) = ۲.۲۲۱ (۱.۱۷۳–۴.۲۰۷), adjusted p value = ۰.۰۲۶). The rs۱۳۳۳۰۴۸ was associated with MDDs in dominant, recessive, and multiplicative models. The selected SNPs were not in linkage disequilibrium (D′ statistic۰.۲۳, r۲ = ۰.۰۵). Haplotype analyses have shown that T A haplotype block (rs۱۳۳۳۰۴۵ and rs۱۳۳۳۰۴۸ 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.Conclusion: 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.