Polymorphisms in seizure 6-like gene are associated with bipolar disorder I: Evidence of gene¡Ágender interaction

详细信息    查看全文

• 作者：Chun Xu^a ; ^{chun.xu@ttuhsc.edu} ; Jerald E. Mullersman^b ; Liang Wang^c ; Brenda Bin Su^d ; ChunXiang Mao^e ; Yolanda Posada^f ; Cynthia Camarillo^a ; Yu Mao^a ; Michael A. Escamilla^a ; Ke-Sheng Wang^c ; ^{wangk@etsu.edu}
• 关键词：SEZ6L ; Bipolar disorder ; Gender differences ; Susceptibility
• 刊名：Journal of Affective Disorders
• 出版年：2013
• 出版时间：15 February, 2013
• 年：2013
• 卷：145
• 期：1
• 页码：95-99
• 全文大小：409 K

文摘

Background

Previous reports have suggested that there may be gene¡Ágender 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.

Methods

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.

Results

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¡Á10^?4) and the strongest gene¡Ágender interaction in influencing BD-I (P=9.16¡Á10^?5).

Limitations

The findings of this study need to be replicated in independent samples.

Conclusions

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.