RATIONALE Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. OBJECTIVE To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. METHODS Associations of n-3 PUFA biomarkers (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N = 16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N = 11,962) and replicated in one cohort (N = 1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNP associations and their interactions with n-3 PUFAs. RESULTS DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P2df = 9.4 × 10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency, ∼80%) was associated with lower FVC (PSNP = 2.1 × 10-9; βSNP = -161.0 ml), and the association was attenuated by higher DHA levels (PSNP×DHA interaction = 2.1 × 10-7; βSNP×DHA interaction = 36.2 ml). CONCLUSIONS We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction.

中文翻译：

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Omega-3 脂肪酸和全基因组相互作用分析揭示了 DPP10-肺功能关联。

基本原理 Omega-3 多不饱和脂肪酸 (n-3 PUFA) 具有抗炎特性，可能有益于患有肺部健康的成年人。目的 研究 n-3 PUFA 与肺功能测试 (PFT) 肺活量测量的关联，并确定潜在的遗传易感性。方法 在七项荟萃分析中，使用 PFT（FEV1、FVC 和 FEV1/FVC）评估 n-3 PUFA 生物标志物（α-亚麻酸、二十碳五烯酸、二十二碳五烯酸 [DPA] 和二十二碳六烯酸 [DHA]）的关联来自基因组流行病学联盟心脏和衰老研究队列的队列（N = 16,134 欧洲或非洲血统）。PFT 相关的 n-3 PUFA 在四个最大队列 (N = 11,962) 中进行全基因组相互作用分析，并在一个队列 (N = 1,687) 中重复。使用 SNP 关联及其与 n-3 PUFA 相互作用的联合 2 自由度 (2df) 荟萃分析来组合特定队列的结果。结果 DPA 和 DHA 与 FEV1 和 FVC 呈正相关（P < 0.025），有证据表明吸烟和性别对效果有影响。全基因组分析发现，当与 DHA 相互作用时，rs11693320（内含子 DPP10 SNP）与 FVC 存在新的关联，并且该发现得到了重复（在发现和复制队列中 P2df = 9.4 × 10-9）。rs11693320-A 等位基因（频率，~80%）与较低的 FVC 相关（PSNP = 2.1 × 10-9；βSNP = -161.0 ml），并且这种关联因较高的 DHA 水平而减弱（PSNP×DHA 相互作用 = 2.1 × 10-7；βSNP×DHA相互作用=36.2ml）。结论 我们证实了 n-3 PUFA 对肺功能的有益作用。通过对全基因组 n-3 PUFA 相互作用进行建模，我们发现了一种新的 DPP10 SNP 与 FVC 的关联，在忽略这种相互作用的大型研究中无法检测到这种关联。