AIMS/HYPOTHESIS Epidemiological data on the associations of circulating fatty acid levels with type 2 diabetes are inconsistent. We conducted a two-sample Mendelian randomisation study to explore the causal associations of plasma levels of ten fatty acids with type 2 diabetes and glycaemic traits. METHODS Thirteen SNPs associated with circulating levels of ten individual fatty acids at the genome-wide significance level (p < 5 × 10-8) were selected as instrumental variables for the exposures. For the outcomes, summary-level data were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for type 2 diabetes (898,130 individuals) and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the glycaemic traits (up to 46,186 non-diabetic individuals). The inverse-variance weighted method was used for analyses. RESULTS Genetic predisposition to higher plasma levels of eight of the ten fatty acids were statistically significantly associated with lower or higher odds of type 2 diabetes. The OR per one SD increment of each fatty acid was 0.93 (95% CI 0.90, 0.96; p = 2.21 × 10-5) for α-linolenic acid, 0.96 (95% CI 0.94, 0.98; p = 1.85 × 10-4) for linoleic acid, 0.86 (95% CI 0.81, 0.91; p = 6.68 × 10-7) for palmitoleic acid, 0.87 (95% CI 0.81, 0.93; p = 2.21 × 10-5) for oleic acid, 1.08 (95% CI 1.03, 1.12; p = 0.002) for eicosapentaenoic acid, 1.04 (95% CI 1.02, 1.07; p = 0.001) for docosapentaenoic acid, 1.03 (95% CI 1.02, 1.05; p = 2.51 × 10-5) for arachidonic acid and 1.09 (95% CI 1.03, 1.15; p = 0.003) for stearic acid. The same eight fatty acids were also associated with fasting glucose levels and HOMA-B. The associations, except that for palmitoleic acid, were driven by variants in FADS1/2. CONCLUSIONS/INTERPRETATION Genetic predisposition to higher circulating levels of eight out of ten fatty acids was associated with type 2 diabetes, fasting glucose and islet beta cell function. However, the associations, except that for palmitoleic acid, were driven by variants in FADS1/2, which encode enzymes with a key role in fatty acid metabolism.

中文翻译：

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与血浆脂肪酸相关的遗传变异与2型糖尿病和血糖性状的关联：孟德尔随机研究。

目的/假设关于循环脂肪酸水平与2型糖尿病的关联的流行病学数据不一致。我们进行了两次抽样的孟德尔随机研究，以探讨10种脂肪酸的血浆水平与2型糖尿病和血糖特征之间的因果关系。方法选择13种与全基因组显着性水平（p <5×10-8）的10种单独脂肪酸的循环水平相关的SNPs作为暴露的工具变量。对于结果，摘要级别的数据来自2型糖尿病的糖尿病遗传学复制和荟萃分析（DIAGRAM）联盟（898,130个人）以及糖尿病和糖尿病相关的葡萄糖和胰岛素相关性状联盟的荟萃分析（MAGIC）。血糖特征（多达46,186名非糖尿病患者）。使用方差逆加权方法进行分析。结果十种脂肪酸中的八种具有较高血浆水平的遗传易感性，与2型糖尿病的较低或较高的发生机率在统计学上显着相关。每种脂肪酸的每SD增量OR分别为0.93（95％CI 0.90，0.96; p = 2.21×10-5），0.96（95％CI 0.94，0.98; p = 1.85×10-4 ）对于亚油酸，对于棕榈油酸为0.86（95％CI 0.81，0.91; p = 6.68×10-7），对于油酸为0.87（95％CI 0.81，0.93; p = 2.21×10-5），对于油酸，1.08（95二十碳五烯酸的％CI 1.03，1.12; p = 0.002），二十二碳五烯酸的1.04（95％CI 1.02，1.07; p = 0.001），花生四烯酸的1.03（95％CI 1.02，1.05; p = 2.51×10-5）酸和硬脂酸的1.09（95％CI 1.03，1.15; p = 0.003）。相同的八种脂肪酸也与空腹血糖水平和HOMA-B有关。除棕榈油酸外，该关联是由FADS1 / 2的变体驱动的。结论/解释遗传易感性导致较高的循环水平（十分之八的脂肪酸）与2型糖尿病，空腹血糖和胰岛β细胞功能有关。但是，除棕榈油酸外，这种关联是由FADS1 / 2的变体驱动的，该变体编码在脂肪酸代谢中起关键作用的酶。