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

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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 (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 SNPassociations and their interactions with n-3PUFAs. 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 (P-2df = 9.4 x 10(-9) across discovery and replication cohorts). The rs11693320-A allele (frequency, similar to 80%) was associated with lower FVC (P-SNP = 2.1 x 10(-9); beta(SNP) = 2161.0 ml), and the association was attenuated by higher DHA levels (P-SNPxDHA interaction = 2.1x10(-7); beta(SNPxDHA 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.
Keywords
FEV1, FVC, smoking, genome-wide association study, omega-3 fatty acids, OBSTRUCTIVE PULMONARY-DISEASE, GENE-ENVIRONMENT INTERACTION, FATTY-ACIDS, LUNG-FUNCTION, DOCOSAHEXAENOIC ACID, NATIONAL-HEALTH, ASTHMA, SMOKING, STATES, METAANALYSIS

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Chicago
Xu, Jiayi, Nathan C Gaddis, Traci M Bartz, Ruixue Hou, Ani W Manichaikul, Nathan Pankratz, Albert V Smith, et al. 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.
APA
Xu, Jiayi, Gaddis, N. C., Bartz, T. M., Hou, R., Manichaikul, A. W., Pankratz, N., Smith, A. V., et al. (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.
Vancouver
1.
Xu J, Gaddis NC, Bartz TM, Hou R, Manichaikul AW, Pankratz N, et al. Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2019;199(5):631–42.
MLA
Xu, Jiayi et al. “Omega-3 Fatty Acids and Genome-wide Interaction Analyses Reveal DPP10-pulmonary Function Association.” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 199.5 (2019): 631–642. Print.
@article{8604696,
  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 (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 SNPassociations and their interactions with n-3PUFAs. 
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 (P-2df = 9.4 x 10(-9) across discovery and replication cohorts). The rs11693320-A allele (frequency, similar to 80%) was associated with lower FVC (P-SNP = 2.1 x 10(-9); beta(SNP) = 2161.0 ml), and the association was attenuated by higher DHA levels (P-SNPxDHA interaction = 2.1x10(-7); beta(SNPxDHA 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.},
  author       = {Xu, Jiayi and Gaddis, Nathan C and Bartz, Traci M and Hou, Ruixue and Manichaikul, Ani W and Pankratz, Nathan and Smith, Albert V and Sun, Fangui and Terzikhan, Natalie and Markunas, Christina A and Patchen, Bonnie K and Schu, Matthew and Beydoun, May A and Brusselle, Guy and Eiriksdottir, Gudny and Zhou, Xia and Wood, Alexis C and Graff, Mariaelisa and Harris, Tamara B and Ikram, M Arfan and Jacobs, David R, Jr and Launer, Lenore J and Lemaitre, Rozenn N and O'Connor, George T and Oelsner, Elizabeth C and Psaty, Bruce M and Ramachandran , Vasan S and Rohde, Rebecca R and Rich, Sstephen S and Rotter, Jerome I and Seshadri, Sudha and Smith, Lewis J and Tiemeier, Henning and Tsai, Michael Y and Uitterlinden, Andre G and Voruganti, V Saroja and Xu, Hanfei and Zilhão, Nuno R and Fornage, Myriam and Zillikens, M Carola and London, Stephanie J and Barr, R Graham and Dupuis, Josée and Gharib, Sina A and Gudnason, Vilmundur and Lahousse, Lies and North, Kari E and Steffen, Lyn M and Cassano, Patricia A and Hancock, Dana B},
  issn         = {1073-449x},
  journal      = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
  keywords     = {FEV1,FVC,smoking,genome-wide association study,omega-3 fatty acids,OBSTRUCTIVE PULMONARY-DISEASE,GENE-ENVIRONMENT INTERACTION,FATTY-ACIDS,LUNG-FUNCTION,DOCOSAHEXAENOIC ACID,NATIONAL-HEALTH,ASTHMA,SMOKING,STATES,METAANALYSIS},
  language     = {eng},
  number       = {5},
  pages        = {631--642},
  title        = {Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association},
  url          = {http://dx.doi.org/10.1164/rccm.201802-0304oc},
  volume       = {199},
  year         = {2019},
}

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