Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10–pulmonary function association

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 IkramDavid 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, Dana B. Hancock

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 (a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV 1 , FVC, and FEV 1 /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 FEV 1 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 (P 2df = 9.4 3 10 29 across discovery and replication cohorts). The rs11693320-A allele (frequency, z80%) was associated with lower FVC (P SNP = 2.1 3 10 29 ; b SNP = 2161.0 ml), and the association was attenuated by higher DHA levels (P SNP 3DHA interaction = 2.1 3 10 27 ; b SNP 3DHA 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.

Original languageEnglish (US)
Pages (from-to)631-642
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Volume199
Issue number5
DOIs
StatePublished - Mar 1 2019

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Keywords

  • FEV
  • FVC
  • Genome-wide association study
  • Omega-3 fatty acids
  • Smoking

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Xu, J., Gaddis, N. C., Bartz, T. M., Hou, R., Manichaikul, A. W., Pankratz, N., Smith, A. V., Sun, F., Terzikhan, N., Markunas, C. A., Patchen, B. K., Schu, M., Beydoun, M. A., Brusselle, G. G., Eiriksdottir, G., Zhou, X., Wood, A. C., Graff, M., Harris, T. B., ... Hancock, D. B. (2019). Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10–pulmonary function association. American journal of respiratory and critical care medicine, 199(5), 631-642. https://doi.org/10.1164/rccm.201802-0304OC