Author
XU, JIAYI - Cornell University | |
GADDIS, NATHAN - Rti International, Usa | |
BARTZ, TRACI - University Of Washington | |
HOU, RUIXUE - University Of North Carolina | |
MANICHAIKUL, ANI - University Of Virginia | |
PANKRATZ, NATHAN - University Of Minnesota | |
SMITH, ALBERT - University Of Michigan | |
SUN, FANGUI - Boston University School Of Public Health | |
TERZIKHAN, NATALIE - Ghent University | |
MARKUNAS, CHRISTINA - Rti International, Usa | |
PATCHEN, BONNIE - Cornell University | |
SCHU, MATTHEW - Rti International, Usa | |
BEYDOUN, MAY - Johns Hopkins School Of Public Health | |
BRUSSELLE, GUY - Ghent University | |
EIRIKSDOTTIR, GUDNY - Icelandic Heart Association | |
ZHOU, XIA - University Of Minnesota | |
WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC) | |
GRAFF, MARIAELISA - University Of North Carolina | |
HARRIS, TAMARA - National Institute On Aging (NIA, NIH) | |
IKRAM, M - Erasmus Medical Center | |
JACOBS JR, DAVID - University Of Minnesota | |
LAUNER, LENORE - National Institute On Aging (NIA, NIH) | |
LEMAITRE, ROZENN - University Of Washington | |
O'CONNOR, GEORGE - Boston University Medical School | |
OELSNER, ELIZABETH - Columbia University - New York | |
PSATY, BRUCE - University Of Washington | |
RAMACHANDRAN, VASAN - Boston University Medical School | |
ROHDE, REBECCA - University Of North Carolina | |
RICH, STEPHEN - University Of Virginia | |
ROTTER, JEROME - Harbor-Ucla Medical Center | |
SESHADRI, SUDHA - Boston University | |
SMITH, LEWIS - Northwestern University | |
TEIMEIER, HENNING - Erasmus Medical Center | |
TSAI, MICHAEL - University Of Minnesota | |
UITTERLINDEN, ANDRE - Erasmus Medical Center | |
VORUGANTI, V - University Of North Carolina | |
XU, HANFEI - Boston University School Of Public Health | |
ZILHÃO, NUNO - Icelandic Heart Association | |
FORNAGE, MYRIAM - University Of Texas Health Science Center | |
ZILLIKENS, M - Netherlands Genomics Initiative | |
LONDON, STEPHANIE - National Institute Of Environmental Health Sciences (NIEHS, NIH) | |
BARR, R - Columbia University - New York | |
DUPUIS, JOSÉE - Boston University School Of Public Health | |
GHARIB, SINA - University Of Washington | |
GUDNASON, VILMUNDUR - Icelandic Heart Association | |
LAHOUSSE, LIES - Erasmus Medical Center | |
NORTH, KARI - University Of North Carolina | |
STEFFEN, LYN - University Of Minnesota | |
CASSANO, PATRICIA - Cornell University | |
HANCOCK, DANA - Rti International, Usa |
Submitted to: American Journal of Respiratory and Critical Care Medicine
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/7/2018 Publication Date: 9/10/2018 Citation: 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., Ikram, M.A., Jacobs Jr, D.R., Launer, L.J., Lemaitre, R.N., O'Connor, G., Oelsner, E.C., Psaty, B.M., Ramachandran, V.S., Rohde, R.R., Rich, S.S., Rotter, J.I., Seshadri, S., Smith, L.J., Teimeier, H., Tsai, M.Y., Uitterlinden, A.G., Voruganti, V.S., Xu, H., Zilhão, N.R., Fornage, M., Zillikens, M.C., London, S.J., Barr, R.G., Dupuis, J., Gharib, S.A., Gudnason, V., Lahousse, L., North, K.E., Steffen, L.M., Cassano, P.A., Hancock, D.B. 2018. Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.201802-0304OC. DOI: https://doi.org/10.1164/rccm.201802-0304OC Interpretive Summary: Obesity is associated with inflammation and a significant co-morbidity is decreased pulmonary health. Omega-3 poly-unsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could help adults with chronic inflammation and decreased pulmonary health. However, few population-based studies have looked at the relationships between n-3 PUFAs and pulmonary function. In addition, although smokers have higher inflammation burden on average, no studies have examined if smoking modifies these relationships. Moreover, pulmonary function measures are heritable, with over 100 genetic markers identified through genome-wide association studies. Yet, to date no studies have examined the evidence for interactions between genetic variants and n-3 PUFAs on pulmonary function. Typically, studies looking at the effects ofn-3 PUFAs with disease risk use self-reported questionnaires of PUFA intake, which can introduce reporting bias and thus not provide a good assessment. To address this, we examined the relationships between biomarkers of n-3 PUFA intake in the blood and pulmonary function tests (PFTs). We used data from seven cohort studies participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, which included 16,134 participants. First we established relationships between n-3 PUFA biomarkers and pulmonary function tests. Then, we tested genome-wide interactions between genetic variants and the n-3 PUFA biomarkers on PFT measures. Results showed a greater beneficial effect of n-3 PUFAs biomarkers, especially one of them (docosahexaenoic acid or DHA), on pulmonary function in current smokers. In addition, a specific genetic marker (DPP10) was related with forced vital capacity. This relationship was not found in standard genome-wide analyses. It was only discovered after incorporating the environmental variable of n-3 PUFA biomarker levels. The results of this study are important as they contribute to the evidence base needed to provide targeted dietary advice for COPD prevention. Technical Abstract: Omega-3 poly-unsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. 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 [FEV1], forced vital capacity [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 single nucleotide polymorphism (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=9.4X10-9 across discovery and replication cohorts). The rs11693320-A allele (frequency~80%) was associated with lower FVC (PSNP=2.1X10**-9; BetaSNP= -161.0mL), and the association was attenuated by higher DHA levels (PSNPXDHA interaction=2.1X10**-7; BetaSNPXDHA interaction=36.2mL). 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. |