TY - JOUR
T1 - Sex-specific effects of gain-of-function P2RX7 variation on bipolar disorder
AU - Winham, Stacey J.
AU - Bobo, William V.
AU - Liu, Jiajia
AU - Coombes, Brandon
AU - Backlund, Lena
AU - Frye, Mark A.
AU - Biernacka, Joanna M.
AU - Schalling, Martin
AU - Lavebratt, Catharina
N1 - Publisher Copyright:
© 2018
PY - 2019/2/15
Y1 - 2019/2/15
N2 - Background: Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder. Methods: We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset. Results: P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males. Neither P2RX7 variants associated with rapid cycling among bipolar patients. Limitations: Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available. Conclusion: The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects.
AB - Background: Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder. Methods: We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset. Results: P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males. Neither P2RX7 variants associated with rapid cycling among bipolar patients. Limitations: Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available. Conclusion: The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects.
KW - Bipolar disorder
KW - P2RX7
KW - Rapid cycling
KW - Sex differences
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U2 - 10.1016/j.jad.2018.11.007
DO - 10.1016/j.jad.2018.11.007
M3 - Article
C2 - 30445384
AN - SCOPUS:85056485195
SN - 0165-0327
VL - 245
SP - 597
EP - 601
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -