Genetically Determined Levels of Serum Metabolites and Risk of Neuroticism: A Mendelian Randomization Study.
Genetically Determined Levels of Serum Metabolites and Risk of Neuroticism: A Mendelian Randomization Study.
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基因决定的血清代谢物水平和神经质风险：孟德尔随机研究
DOI：
10.1093/ijnp/pyaa062
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发表时间：
2021-01-20
期刊：
影响因子：
--
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Qian L;Fan Y;Gao F;Zhao B;Yan B;Wang W;Yang J;Ma X
摘要背景神经质是多种社会和行为结果的强有力预测因子，但其病因仍不清楚。我们的研究旨在使用孟德尔随机化（MR）方法对血清代谢组表型对神经质风险的因果影响进行全面调查。方法以486个代谢性状的遗传关联作为暴露，以神经质的大规模全基因组关联研究的数据作为结果。对于MR分析，我们使用标准的逆方差加权（IVW）方法进行主要MR分析，并使用3种额外的MR方法（MR-Egger、加权中位数、MR多效性残差和和离群值）进行敏感性分析。结果我们的研究确定了31种可能对神经质有因果关系的代谢物。在31种代谢物中，尿酸和副黄嘌呤在所有MR方法中均与神经质显著相关。使用单核苷酸多态性作为工具变量，尿酸增加1-SD与神经质风险降低约30（OR：0.77; 95%CI：0.62-0.95; PIVW = 0.0145），而副黄嘌呤增加1-SD与神经质风险增加7%相关。（OR：1.07; 95% CI：1.01-1.12; PIVW = .0145）。讨论我们的研究表明，尿酸水平升高与神经质的风险降低有关，而副黄嘌呤则表现出相反的效果。我们的研究通过将代谢组学与基因组学相结合来帮助理解神经质的发病机制，提供了新的见解。
Abstract Background Neuroticism is a strong predictor for a variety of social and behavioral outcomes, but the etiology is still unknown. Our study aims to provide a comprehensive investigation of causal effects of serum metabolome phenotypes on risk of neuroticism using Mendelian randomization (MR) approaches. Methods Genetic associations with 486 metabolic traits were utilized as exposures, and data from a large genome-wide association study of neuroticism were selected as outcome. For MR analysis, we used the standard inverse-variance weighted (IVW) method for primary MR analysis and 3 additional MR methods (MR-Egger, weighted median, and MR pleiotropy residual sum and outlier) for sensitivity analyses. Results Our study identified 31 metabolites that might have causal effects on neuroticism. Of the 31 metabolites, uric acid and paraxanthine showed robustly significant association with neuroticism in all MR methods. Using single nucleotide polymorphisms as instrumental variables, a 1-SD increase in uric acid was associated with approximately 30% lower risk of neuroticism (OR: 0.77; 95% CI: 0.62–0.95; PIVW = 0.0145), whereas a 1-SD increase in paraxanthine was associated with a 7% higher risk of neuroticism (OR: 1.07; 95% CI: 1.01–1.12; PIVW = .0145). Discussion Our study suggested an increased level of uric acid was associated with lower risk of neuroticism, whereas paraxanthine showed the contrary effect. Our study provided novel insight by combining metabolomics with genomics to help understand the pathogenesis of neuroticism.
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影响因子：
16.4
作者：
Lahey, Benjamin B.
通讯作者：
Lahey, Benjamin B.
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
14.9
作者：
Frolkis A;Knox C;Lim E;Jewison T;Law V;Hau DD;Liu P;Gautam B;Ly S;Guo AC;Xia J;Liang Y;Shrivastava S;Wishart DS
通讯作者：
Wishart DS