A genome-wide association study identifies 41 loci associated with eicosanoid levels.
A genome-wide association study identifies 41 loci associated with eicosanoid levels.
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DOI：
10.1038/s42003-023-05159-5
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发表时间：
2023-07-31
影响因子：
5.9
通讯作者：
Grams, Morgan E.
中科院分区：
文献类型：
--
作者：
Rhee, Eugene P.;Surapaneni, Aditya L.;Schlosser, Pascal;Alotaibi, Mona;Yang, Yueh-ning;Coresh, Josef;Jain, Mohit;Cheng, Susan;Yu, Bing;Grams, Morgan E.
类二十烷酸是多不饱和脂肪酸的生物活性衍生物，与健康和疾病具有广泛的相关性。我们报告了一项针对社区动脉粥样硬化风险研究的 8406 名参与者进行的全基因组关联研究，确定了与 92 种类二十烷酸和相关代谢物相关的 41 个基因座。这些发现强调了类二十烷酸生物合成所需的基因座，包括 FADS1-3、ELOVL2 和许多 CYP450 基因座。此外，显着的关联涉及类二十烷酸调节中的一系列非氧化脂质代谢过程，包括 PKD2L1/SCD 和涉及脂肪酰辅酶 A 代谢的几个位点。此外，我们的研究结果强调了选择的清除机制，例如通过 SLCO1B1 编码的肝脏转运蛋白。最后，我们确定了与阿司匹林和非甾体抗炎药使用相关的类二十烷酸，并证明了遗传变异的重大影响，即使对于与药物相关的类二十烷酸也是如此。这些发现揭示了类二十烷酸代谢的已知和未知方面，并激发了人们对几种基因-类二十烷酸关联作为人类疾病的潜在功能参与者的兴趣。对来自社区动脉粥样硬化风险 (ARIC) 研究的 8406 名参与者进行的全基因组关联研究确定了与 92 种类二十烷酸和相关代谢物相关的 41 个基因座。
Eicosanoids are biologically active derivatives of polyunsaturated fatty acids with broad relevance to health and disease. We report a genome-wide association study in 8406 participants of the Atherosclerosis Risk in Communities Study, identifying 41 loci associated with 92 eicosanoids and related metabolites. These findings highlight loci required for eicosanoid biosynthesis, including FADS1-3, ELOVL2, and numerous CYP450 loci. In addition, significant associations implicate a range of non-oxidative lipid metabolic processes in eicosanoid regulation, including at PKD2L1/SCD and several loci involved in fatty acyl-CoA metabolism. Further, our findings highlight select clearance mechanisms, for example, through the hepatic transporter encoded by SLCO1B1. Finally, we identify eicosanoids associated with aspirin and non-steroidal anti-inflammatory drug use and demonstrate the substantial impact of genetic variants even for medication-associated eicosanoids. These findings shed light on both known and unknown aspects of eicosanoid metabolism and motivate interest in several gene-eicosanoid associations as potential functional participants in human disease. A genome-wide association study in 8406 participants from the Atherosclerosis Risk in Communities (ARIC) Study identifies 41 loci associated with 92 eicosanoids and related metabolites.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
30.8
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影响因子：
30.8
作者：
Kettunen, Johannes;Tukiainen, Taru;Sarin, Antti-Pekka;Ortega-Alonso, Alfredo;Tikkanen, Emmi;Lyytikainen, Leo-Pekka;Kangas, Antti J.;Soininen, Pasi;Wuertz, Peter;Silander, Kaisa;Dick, Danielle M.;Rose, Richard J.;Savolainen, Markku J.;Viikari, Jorma;Kahonen, Mika;Lehtimaki, Terho;Pietilainen, Kirsi H.;Inouye, Michael;McCarthy, Mark I.;Jula, Antti;Eriksson, Johan;Raitakari, Olli T.;Salomaa, Veikko;Kaprio, Jaakko;Jarvelin, Marjo-Riitta;Peltonen, Leena;Perola, Markus;Freimer, Nelson B.;Ala-Korpela, Mika;Palotie, Aarno;Ripatti, Samuli
通讯作者：
Ripatti, Samuli
影响因子：
16.6
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通讯作者：
--
影响因子：
64.5
作者：
Astle, William J.;Elding, Heather;Soranzo, Nicole
通讯作者：
Soranzo, Nicole