Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study.
Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study.
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DOI：
10.1186/s12967-023-04202-7
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发表时间：
2023-06-07
影响因子：
7.4
通讯作者：
Lu, Jieli
中科院分区：
文献类型：
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作者：
Hu, Chunyan;Zhou, Yulin;Wu, Xueyan;Jia, Xiaojing;Zhu, Yuanyue;Zheng, Ruizhi;Wang, Shuangyuan;Lin, Lin;Qi, Hongyan;Lin, Hong;Li, Mian;Wang, Tiange;Zhao, Zhiyun;Xu, Min;Xu, Yu;Chen, Yuhong;Ning, Guang;Borges, Maria-Carolina;Wang, Weiqing;Zheng, Jie;Bi, Yufang;Lu, Jieli
关键词：
观察性研究和传统的孟德尔随机化（MR）研究显示，没有确凿的证据支持omega-3脂肪酸和2型糖尿病之间的关联。我们的目的是评估ω-3脂肪酸对2型糖尿病（T2 DM）的因果关系，以及连接两者的不同中间表型。使用来自UK Biobank的最近一项omega-3脂肪酸全基因组关联研究（GWAS）（N = 114，999）的遗传仪器和来自欧洲血统的大规模T2 DM GWAS（62，892例病例和596，424例对照）的结局数据进行双样本MR。应用MR-Clust确定影响T2 DM的ω-3脂肪酸的聚类遗传工具。两步MR分析用于鉴定将omega-3脂肪酸与T2 DM联系起来的潜在中间表型（例如血糖性状）。单变量MR显示omega-3脂肪酸对T2 DM的异质性影响。使用MR-Clust确定了omega-3脂肪酸和T2 DM之间至少两种多效性效应。对于使用7种仪器的第1组，增加omega-3脂肪酸可降低T2 DM风险（OR：0.52，95%CI 0.45-0.59），并降低HOMA-IR（β =-0.13，SE = 0.05，P = 0.02）。相反，使用聚类2中的10种仪器进行的MR分析显示，增加omega-3脂肪酸会增加T2 DM风险（OR：1.10; 95%CI 1.06-1.15），并降低HOMA-B（β = − 0.04，SE = 0.01，P = 4.52 × 10-5）。两步MR表明，增加ω-3脂肪酸水平通过降低第1组的HOMA-IR降低T2 DM风险，而通过降低第2组的HOMA-B增加T2 DM风险。这项研究提供的证据支持两种不同的多效性效应的ω-3脂肪酸对T2 DM的风险影响不同的基因簇，这可以部分解释的ω-3脂肪酸对胰岛素抵抗和β细胞功能障碍的不同影响。在未来的遗传和临床研究中，需要仔细考虑omega-3脂肪酸变体的多效性特征及其与T2 DM的复杂关系。在线版本包含补充材料，可通过10.1186/s12967-023-04202-7获得。
Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10–5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies. The online version contains supplementary material available at 10.1186/s12967-023-04202-7.
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影响因子：
2
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan N;Thompson J
通讯作者：
Thompson J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
海洋N-3脂肪酸和心血管疾病和癌症的预防。
DOI：
10.1056/nejmoa1811403
发表时间：
2019-01-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Manson JE;Cook NR;Lee IM;Christen W;Bassuk SS;Mora S;Gibson H;Albert CM;Gordon D;Copeland T;D'Agostino D;Friedenberg G;Ridge C;Bubes V;Giovannucci EL;Willett WC;Buring JE;VITAL Research Group
通讯作者：
VITAL Research Group
影响因子：
7.1
作者：
Djousse, Luc;Gaziano, J. Michael;Lee, I-Min
通讯作者：
Lee, I-Min
影响因子：
3.5
作者：
通讯作者：
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