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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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Citation

Please use this url to cite or link to this publication:

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, vol. 199, no. 5, 2019, pp. 631–42.
APA
Xu, J., Gaddis, N. C., Bartz, T. M., Hou, R., Manichaikul, A. W., Pankratz, N., … 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.
Chicago author-date
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): 631–42.
Chicago author-date (all authors)
Xu, Jiayi, 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 Brusselle, Gudny Eiriksdottir, Xia Zhou, Alexis C Wood, Mariaelisa Graff, Tamara B Harris, M Arfan Ikram, David R Jacobs Jr, Lenore J Launer, Rozenn N Lemaitre, George T O’Connor, Elizabeth C Oelsner, Bruce M Psaty, Vasan S Ramachandran, Rebecca R Rohde, Sstephen S Rich, Jerome I Rotter, Sudha Seshadri, Lewis J Smith, Henning Tiemeier, Michael Y Tsai, Andre 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. 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.
IEEE
[1]
J. Xu et al., “Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association,” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 199, no. 5, pp. 631–642, 2019.
@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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