AUTHOR=Ullah Ata , Long Xi , Mat Wai-Kin , Hu Taobo , Khan Muhammad Ismail , Hui Li , Zhang Xiangyang , Sun Peng , Gao Mingzhou , Wang Jieqiong , Wang Haijun , Li Xia , Sun Wenjun , Qiao Mingqi , Xue Hong 

TITLE=Highly Recurrent Copy Number Variations in GABRB2 Associated With Schizophrenia and Premenstrual Dysphoric Disorder

JOURNAL=Frontiers in Psychiatry

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00572

DOI=10.3389/fpsyt.2020.00572

ISSN=1664-0640

ABSTRACT=<sec><title>Objective</title><p>Although single-nucleotide polymorphisms in <italic>GABRB2</italic>, the gene encoding for GABA<sub>A</sub> receptors β2 subunit, have been associated with schizophrenia (SCZ), it is unknown whether there is any association of copy number variations (CNVs) in this gene with either SCZ or premenstrual dysphoric disorder (PMDD).</p></sec><sec><title>Methods</title><p>In this study, the occurrences of the recurrent CNVs esv2730987 in Intron 6 and nsv1177513 in Exon 11 of <italic>GABRB2</italic> in Chinese and German SCZ, and Chinese PMDD patients were compared to controls of same ethnicity and gender by quantitative PCR (qPCR).</p></sec><sec><title>Results</title><p>The results demonstrated that copy-number-gains were enriched in both SCZ and PMDD patients with significant odds ratios (OR). For combined-gender SCZ patients versus controls, about two-fold increases were observed in both ethnic groups at both esv2730987 (OR = 2.15, <italic>p =</italic> 5.32E−4 in Chinese group; OR = 2.79, <italic>p =</italic> 8.84E−3 in German group) and nsv1177513 (OR = 3.29, <italic>p =</italic> 1.28E−11 in Chinese group; OR = 2.44, <italic>p =</italic> 6.17E−5 in German group). The most significant copy-number-gains were observed in Chinese females at nsv1177513 (OR = 3.41), and German females at esv2730987 (OR=3.96). Copy-number-gains were also enriched in Chinese PMDD patients versus controls at esv2730987 (OR = 10.53, <italic>p =</italic> 4.34E−26) and nsv1177513 (OR = 2.39, <italic>p =</italic> 3.19E−5).</p></sec><sec><title>Conclusion</title><p>These findings established for the first time the association of highly recurrent CNVs with SCZ and PMDD, suggesting the presence of an overlapping genetic basis with shared biomarkers for these two common psychiatric disorders.</p></sec>