Author Correction: Proteogenomic links to human metabolic diseases.
Author Correction: Proteogenomic links to human metabolic diseases.
复制标题
作者更正：蛋白质基因组与人类代谢疾病的联系。
DOI：
10.1038/s42255-023-00785-z
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发表时间：
2023
影响因子：
20.8
通讯作者：
Koprulu M
中科院分区：
文献类型：
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作者：
Koprulu M
研究作为基因组和表型组之间的中间层的血浆蛋白质组具有识别新的疾病过程的潜力。在这里，我们使用基于抗体的测定法对1,180名个体中测量的2,923种血浆蛋白进行了以acis为中心的蛋白质组学分析。我们（1）确定了256个未报道的蛋白质数量性状位点（pQTL）;（2）证明了224个cis-pQTL与575个特定健康结果的共同遗传调控，揭示了显著代谢疾病的例子（如胃泌素释放肽作为2型糖尿病的潜在治疗靶点）;（3）改善40%（n= 192）重叠风险位点的致病基因分配;（4）观察到脂蛋白代谢的TIMD 4等12个蛋白质的cis-pQTLs的表型结果的收敛性和罕见的功能丧失基因负担。我们的研究结果表明，即使在中等规模，将互补蛋白质组学技术与基因组学相结合，以确定具有治疗干预潜力的代谢疾病的新介质的价值。
Studying the plasma proteome as the intermediate layer between the genome and the phenome has the potential to identify new disease processes. Here, we conducted acis-focused proteogenomic analysis of 2,923 plasma proteins measured in 1,180 individuals using antibody-based assays. We (1) identify 256 unreported protein quantitative trait loci (pQTL); (2) demonstrate shared genetic regulation of 224cis-pQTLs with 575 specific health outcomes, revealing examples for notable metabolic diseases (such as gastrin-releasing peptide as a potential therapeutic target for type 2 diabetes); (3) improve causal gene assignment at 40% (n= 192) of overlapping risk loci; and (4) observe convergence of phenotypic consequences ofcis-pQTLs and rare loss-of-function gene burden for 12 proteins, such asTIMD4for lipoprotein metabolism. Our findings demonstrate the value of integrating complementary proteomic technologies with genomics even at moderate scale to identify new mediators of metabolic diseases with the potential for therapeutic interventions.