Association between circulating fatty acid metabolites and asthma risk: a two-sample bidirectional Mendelian randomization study.
Association between circulating fatty acid metabolites and asthma risk: a two-sample bidirectional Mendelian randomization study.
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DOI：
10.1186/s12920-023-01545-4
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发表时间：
2023-05-23
影响因子：
2.7
通讯作者：
中科院分区：
文献类型：
--
作者：
脂肪酸参与了人类广泛的免疫反应。据报道，补充多不饱和脂肪酸有助于缓解哮喘患者的症状和气道炎症，而脂肪酸对哮喘实际风险的影响仍存在争议。本研究采用双样本双向孟德尔随机化（MR）分析，全面调查了血清脂肪酸对哮喘风险的因果关系。提取与123种循环脂肪酸代谢物密切相关的遗传变异作为工具变量，并使用哮喘的大量GWAS数据来测试代谢物对该结果的影响。采用逆方差加权法进行初步MR分析。采用加权中位数、MR-Egger回归、MR-EMO和留一法分析评价异质性和多效性。通过进行多变量MR分析调整潜在混杂因素。还进行了反向MR分析，以估计哮喘对候选脂肪酸代谢产物的因果影响。此外，我们进行了共定位分析，以检查脂肪酸去饱和酶1（FADS 1）基因座内的变异体的多效性之间的显着代谢物性状和哮喘的风险。同时进行顺式eQTL-MR和共定位分析，以确定FADS 1的RNA表达与哮喘之间的关系。在初级MR分析中，遗传学检测的较高的亚甲基平均数与较低的哮喘风险有因果关系，而相反，较高的双烯丙基基团与双键的比率和较高的双烯丙基基团与总脂肪酸的比率与较高的哮喘概率相关。当调整潜在混杂因素时，在多变量MR中获得了一致的结果。然而，在排除与FADS 1基因相关的SNP后，这些影响被完全消除。反向MR也未发现因果关系。共定位分析表明，这三个候选代谢物性状和哮喘可能在FADS 1基因座内共享因果变异。此外，cis-eQTL-MR和共定位分析证明了FADS 1表达和哮喘之间的因果关系和共享的因果变异。我们的研究支持多不饱和脂肪酸特征与哮喘风险之间的负相关性。然而，这种关联在很大程度上归因于FADS 1多态性的影响。考虑到与FADS 1相关的SNP的多效性，应仔细解释这项MR研究的结果。在线版本包含补充材料，可通过10.1186/s12920-023-01545-4获得。
Fatty acids are involved in a wide range of immunological responses in humans. Supplementation of polyunsaturated fatty acids has been reported to help alleviate symptoms and airway inflammation in asthma patients, whereas the effects of fatty acids on the actual risk of asthma remain controversial. This study comprehensively investigated the causal effects of serum fatty acids on asthma risk using two-sample bidirectional Mendelian Randomization (MR) analysis. Genetic variants strongly associated with 123 circulating fatty acid metabolites were extracted as instrumental variables, and a large GWAS data of asthma was used to test effects of the metabolites on this outcome. The inverse-variance weighted method was used for primary MR analysis. The weighted median, MR-Egger regression, MR-PRESSO, and leave-one-out analyses were utilized to evaluate heterogeneity and pleiotropy. Potential confounders were adjusted by performing multivariable MR analyses. Reverse MR analysis was also conducted to estimate the causal effect of asthma on candidate fatty acid metabolites. Further, we performed colocalization analysis to examine the pleiotropy of variants within the fatty acid desaturase 1 (FADS1) locus between the significant metabolite traits and the risk of asthma. Cis-eQTL-MR and colocalization analysis were also performed to determine the association between RNA expression of FADS1 and asthma. Genetically instrumented higher average number of methylene groups was causally associated with a lower risk of asthma in primary MR analysis, while inversely, the higher ratio of bis-allylic groups to double bonds and the higher ratio of bis-allylic groups to total fatty acids, were associated with higher probabilities of asthma. Consistent results were obtained in multivariable MR when adjusted for potential confounders. However, these effects were completely eliminated after SNPs correlated with the FADS1 gene were excluded. The reverse MR also found no causal association. The colocalization analysis suggested that the three candidate metabolite traits and asthma likely share causal variants within the FADS1 locus. In addition, the cis-eQTL-MR and colocalization analyses demonstrated a causal association and shared causal variants between FADS1 expression and asthma. Our study supports a negative association between several PUFA traits and the risk of asthma. However, this association is largely attributed to the influence of FADS1 polymorphisms. The results of this MR study should be carefully interpreted given the pleiotropy of SNPs associated with FADS1. The online version contains supplementary material available at 10.1186/s12920-023-01545-4.
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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：
7.1
作者：
Guasch-Ferre, Marta;Babio, Nancy;Salas-Salvado, Jordi
通讯作者：
Salas-Salvado, Jordi
影响因子：
7.7
作者：
Brion, Marie-Jo A.;Shakhbazov, Konstantin;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
影响因子：
14.2
作者：
Almqvist, Catarina;Garden, Frances;Marks, Guy B.
通讯作者：
Marks, Guy B.
影响因子：
30.8
作者：
Liu, Mengzhen;Jiang, Yu;Stensland, Synne Oien
通讯作者：
Stensland, Synne Oien