Expression quantitative trait locus (eQTL) studies in human liver are crucial for elucidating how genetic variation influences variability in disease risk and therapeutic outcomes and may help guide strategies to obtain maximal efficacy and safety of clinical interventions. Associations between expression microarray and genome-wide genotype data from four human liver eQTL studies (n = 1,183) were analyzed. More than 2.3 million cis-eQTLs for 15,668 genes were identified. When eQTLs were filtered against a list of 1,496 drug response genes, 187,829 cis-eQTLs for 1,191 genes were identified. Additionally, 1,683 sex-biased cis-eQTLs were identified, as well as 49 and 73 cis-eQTLs that colocalized with genome-wide association study signals for blood metabolite or lipid levels, respectively. Translational relevance of these results is evidenced by linking DPYD eQTLs to differences in safety of chemotherapy, linking the sex-biased regulation of PCSK9 expression to anti-lipid therapy, and identifying the G-protein coupled receptor GPR180 as a novel drug target for hypertriglyceridemia.

中文翻译：

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来自 1,183 个人的新肝脏表达定量性状基因座图为药物反应、代谢和性别偏见表型的新表达定量性状基因座提供了证据。

人类肝脏中的表达数量性状基因座 (eQTL) 研究对于阐明遗传变异如何影响疾病风险和治疗结果的变异性至关重要，并且可能有助于指导获得最大疗效和临床干预安全性的策略。分析了来自四项人类肝脏 eQTL 研究 (n = 1,183) 的表达微阵列和全基因组基因型数据之间的关联。鉴定了 15,668 个基因的超过 230 万个 cis-eQTL。当根据 1,496 个药物反应基因的列表过滤 eQTLs 时，鉴定出 1,191 个基因的 187,829 个 cis-eQTLs。此外，还鉴定了 1,683 个有性别偏见的 cis-eQTL，以及分别与血液代谢物或脂质水平的全基因组关联研究信号共定位的 49 和 73 个 cis-eQTL。