METHODS: We conducted in-silico functional analyses by integrating and synthesising information from several publicly available functional genetic datasets and databases including the Genotype-Tissue Expression (GTEx) project and HaploReg.
RESULTS: The findings from this study highlighted TMPRSS15 as the most likely effector gene at the ConLi+Gen lithium response locus. TMPRSS15 encodes enterokinase, a gastrointestinal enzyme responsible for converting trypsinogen into trypsin and thus aiding digestion. Convergent findings from gene-based lookups in human and mouse databases as well as co-expression network analyses of small intestinal RNA-seq data (GTEx) implicated TMPRSS15 in the regulation of intestinal nutrient absorption, including ions like sodium and potassium, which may extend to lithium.
CONCLUSIONS: Although the findings from this study indicated that TMPRSS15 was the most likely effector gene at the ConLi+Gen lithium response locus, the evidence was circumstantial. Thus, the conclusions from this study need to be validated in appropriately designed wet-lab studies.
CONCLUSIONS: The findings from this study are consistent with a model whereby TMPRSS15 impacts the efficacy of lithium treatment in patients with bipolar disorder by modulating intestinal lithium absorption.
方法:我们通过整合和合成来自几个公开的功能遗传数据集和数据库(包括基因型-组织表达(GTEx)项目和HaploReg)的信息进行了计算机功能分析。
结果:这项研究的发现强调了TMPRSS15是ConLiGen锂反应基因座上最可能的效应基因。TMPRSS15编码肠激酶,一种胃肠道酶,负责将胰蛋白酶原转化为胰蛋白酶,从而帮助消化。来自人类和小鼠数据库中基于基因的查找以及小肠RNA-seq数据(GTEx)的共表达网络分析的融合发现表明TMPRSS15参与了肠道营养吸收的调节,包括离子如钠和钾,可能延伸到锂。
结论:尽管这项研究的结果表明,TMPRSS15是ConLiGen锂反应基因座上最有可能的效应基因,证据是间接的。因此,本研究的结论需要在适当设计的湿实验室研究中进行验证.
结论:这项研究的结果与TMPRSS15通过调节肠道锂吸收影响双相情感障碍患者锂治疗疗效的模型一致。