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{Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association
Tuesday,2020-10-27 21:48 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 | 2019 |
| 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, MA, Jacobs, DR, Launer, LJ, Lemaitre, RN, O'Connor, GT, Oelsner, EC, Psaty, BM, Vasan, RS, Rohde, RR, Rich, SS, Rotter, JI, Seshadri, S, Smith, LJ, Tiemeier, H, Tsai, MY, Uitterlinden, AG, Voruganti, VS, Xu, H, Zilh?o, NR, Fornage, M, Zillikens, MC, London, SJ, Barr, RG, Dupuis, J, Gharib, SA, Gudnason, V, Lahousse, L, North, KE, Steffen, LM, Cassano, PA, Hancock, DB |
| Journal | Am J Respir Crit Care Med |
| Volume | 199 |
| Pagination | 631–642 |
| Date Published | 03 |
| Abstract | Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health.\ To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility.\ Associations 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.\ 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 (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).\ 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. |
ePub date:
19/03