Departments of Psychiatry and Neurology Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, and The Center of Excellence in Neuroscience, El Paso, Texas, USA.
J Affect Disord. 2013 Feb 15;145(1):95-9. doi: 10.1016/j.jad.2012.07.017. Epub 2012 Aug 22.
Previous reports have suggested that there may be gene × gender interaction for bipolar disorder (BD)-associated genes/loci at 22q11-13. This study aimed to investigate the associations of SEZ6L genetic variants with bipolar disorder I (BD-I) and to examine gender-specific genetic associations.
605 BD-I Caucasian cases and 1034 controls were selected from the publicly available data of the Whole Genome Association Study of BD. To increase power, an additional 362 Caucasian controls were added to this study from the Genome-Wide Association Study of Schizophrenia. In total, 605 BD-I cases and 1396 controls (934 males and 1067 females) were available for genetic association analysis of 118 SNPs within the SEZ6L gene using PLINK software.
16 SNPs showed significant gene x gender interactions influencing BD-I (P<0.01). In addition, significant differences in the distribution of the alleles for these 16 SNPs were observed between the female BD-I patients and healthy controls (P<0.015) but no significant associations were found for the male sample (P>0.05). The SNP rs4822691 showed the strongest association with BD-I in the female sample (P=2.18 × 10(-4)) and the strongest gene × gender interaction in influencing BD-I (P=9.16 × 10(-5)).
The findings of this study need to be replicated in independent samples.
This is the first demonstration that genetic variants in the SEZ6L gene are associated with BD-I in female patients and provides additional compelling evidence for genetic variation at 22q11-13 that influences BD-I risk. The present findings highlight the gene x gender interactions modifying BD-I susceptibility.
先前的报告表明，22q11-13 上的双相情感障碍（BD）相关基因/基因座可能存在基因×性别相互作用。本研究旨在探讨 SEZ6L 遗传变异与双相情感障碍 I（BD-I）的关联，并检验性别特异性遗传关联。
从 BD 的全基因组关联研究的公开可用数据中选择了 605 例 BD-I 白种人病例和 1034 例对照。为了增加效力，从精神分裂症的全基因组关联研究中又向本研究增加了 362 例白种人对照。总共，使用 PLINK 软件对 SEZ6L 基因内的 118 个 SNP 进行了 605 例 BD-I 病例和 1396 例对照（934 名男性和 1067 名女性）的遗传关联分析。
16 个 SNP 显示出显著的基因×性别相互作用，影响 BD-I（P<0.01）。此外，在女性 BD-I 患者和健康对照之间观察到这些 16 个 SNP 的等位基因分布存在显著差异（P<0.015），但在男性样本中未发现显著关联（P>0.05）。SNP rs4822691 在女性样本中与 BD-I 关联最强（P=2.18 × 10(-4)），在影响 BD-I 方面的基因×性别相互作用最强（P=9.16 × 10(-5)）。
本研究的发现需要在独立样本中得到复制。
这是首次证明 SEZ6L 基因中的遗传变异与女性患者的 BD-I 相关，并为影响 BD-I 风险的 22q11-13 上的遗传变异提供了额外的有力证据。本研究结果突出了修饰 BD-I 易感性的基因×性别相互作用。
