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Omega-3 Fatty Acids and Genome-wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.
Tuesday,2018-09-18 16:23 America/Los_Angeles — ecterry
| Title | Omega-3 Fatty Acids and Genome-wide Interaction Analyses Reveal DPP10-Pulmonary Function Association. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Xu, J, Gaddis, NC, Bartz, TM, Hou, R, Manichaikul, AW, Pankratz, N, Smith, AV, Sun, F, Terzikhan, N, Markunas, CA, Patchen, BK, Schu, M, Beydoun, MA, Brusselle, GG, Eiriksdottir, G, Zhou, X, Wood, AC, Graff, M, Harris, TB, Ikram, AM, Jacobs, DR, Launer, LJ, Lemaitre, RN, O'Connor, G, Oelsner, EC, Psaty, BM, Ramachandran, VS, Rohde, RR, Rich, SS, Rotter, JI, Seshadri, S, Smith, LJ, Tiemeier, H, Tsai, MY, Uitterlinden, AG, V Voruganti, S, Xu, H, Zilhão, NR, Fornage, M, Zillikens, CM, London, SJ, R Barr, G, Dupuis, J, Gharib, SA, Gudnason, V, Lahousse, L, North, KE, Steffen, LM, Cassano, PA, Hancock, DB |
| Journal | Am J Respir Crit Care Med |
| Date Published | 2018 Sep 10 |
| ISSN | 1535-4970 |
| Abstract | <p><b>RATIONALE: </b>Omega-3 poly-unsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.</p><p><b>OBJECTIVE: </b>To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.</p><p><b>METHODS: </b>Associations of n-3 PUFA biomarkers (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (forced expiratory volume in the first second [FEV], forced vital capacity [FVC], and [FEV/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 single nucleotide polymorphism (SNP) associations and their interactions with n-3 PUFAs.</p><p><b>RESULTS: </b>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=9.4×10 across discovery and replication cohorts). The rs11693320-A allele (frequency~80%) was associated with lower FVC (P=2.1×10; β= -161.0mL), and the association was attenuated by higher DHA levels (P=2.1×10; β=36.2mL).</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1164/rccm.201802-0304OC |
| Alternate Journal | Am. J. Respir. Crit. Care Med. |
| PubMed ID | 30199657 |
ePub date:
18/09