• Jiayi Xu, Nathan C Gaddis, Traci M Bartz, Ruixue Hou, Ani W Manichaikul, Nathan Pankratz, Albert V Smith, Fangui Sun, Natalie Terzikhan, Christina A Markunas, Bonnie K Patchen, Matthew Schu, May A Beydoun, Guy G Brusselle, Gudny Eiriksdottir, Xia Zhou, Alexis C Wood, Mariaelisa Graff, Tamara B Harris, M Arfan Ikram, David R Jacobs, Lenore J Launer, Rozenn N Lemaitre, George T O'Connor, Elizabeth C Oelsner, Bruce M Psaty, Ramachandran S Vasan, Rebecca R Rohde, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Lewis J Smith, Henning Tiemeier, Michael Y Tsai, André G Uitterlinden, V Saroja Voruganti, Hanfei Xu, Nuno R Zilhão, Myriam Fornage, M Carola Zillikens, Stephanie J London, R Graham Barr, Josée Dupuis, Sina A Gharib, Vilmundur Gudnason, Lies Lahousse, Kari E North, Lyn M Steffen, Patricia A Cassano, and Dana B Hancock.
• 1 Division of Nutritional Sciences, Cornell University, Ithaca, New York.
• Am. J. Respir. Crit. Care Med. 2019 Mar 1; 199 (5): 631642631-642.

RationaleOmega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.ObjectiveTo investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.MethodsAssociations 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.ResultsDPA 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).ConclusionsWe 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.

39 keywords...

hide…