ANRIL Variants Are Associated with Risk of Neuropsychiatric Conditions
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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.
KeywordsAntisense non-coding RNA in the INK4 locus ANRIL rs1333045 rs1333048 Bipolar disorder Major depressive disorder Methamphetamine addiction
Compliance with ethical standards
Written informed consent was obtained from all enrolled individuals. The study protocol was approved by the ethics committees of Shahid Beheshti Universities of Medical Sciences.
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