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

Jiayi Xu; 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 G. Brusselle; Gudny Eiriksdottir; Xia Zhou; Alexis C. Wood; Mariaelisa Graff; Tamara B. Harris; M. Arfan Ikram; David R. Jacobs; Lenore J. Launer; Rozenn N. Lemaitre; George T. O’Connor; Elizabeth C. Oelsner; Bruce M. Psaty; Ramachandran S. Vasan; Rebecca R. Rohde; Stephen S. Rich; Jerome I. Rotter; Sudha Seshadri; Lewis J. Smith; Henning Tiemeier; Michael Y. Tsai; André 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; Dana B. Hancock

doi:10.1164/rccm.201802-0304OC

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

Jiayi Xu, 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 G. Brusselle, Gudny Eiriksdottir, Xia Zhou, Alexis C. Wood, Mariaelisa Graff, Tamara B. Harris, M. Arfan IkramDavid R. Jacobs, Lenore J. Launer, Rozenn N. Lemaitre, George T. O’Connor, Elizabeth C. Oelsner, Bruce M. Psaty, Ramachandran S. Vasan, Rebecca R. Rohde, Stephen S. Rich, Jerome I. Rotter, Sudha Seshadri, Lewis J. Smith, Henning Tiemeier, Michael Y. Tsai, André 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, Dana B. Hancock

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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 (FEV ₁ , FVC, and FEV ₁ /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 Results: DPA and DHA were positively associated with FEV ₁ 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 3 10 ²⁹ across discovery and replication cohorts). The rs11693320-A allele (frequency, z80%) was associated with lower FVC (P _SNP = 2.1 3 10 ²⁹ ; b _SNP = 2161.0 ml), and the association was attenuated by higher DHA levels (P _SNP 3DHA _interaction = 2.1 3 10 ²⁷ ; b _SNP 3DHA _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.

Original language	English (US)
Pages (from-to)	631-642
Number of pages	12
Journal	American journal of respiratory and critical care medicine
Volume	199
Issue number	5
DOIs	https://doi.org/10.1164/rccm.201802-0304OC
State	Published - Mar 1 2019

Keywords

FEV
FVC
Genome-wide association study
Omega-3 fatty acids
Smoking

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Critical Care and Intensive Care Medicine

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10.1164/rccm.201802-0304OC

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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., ... 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. https://doi.org/10.1164/rccm.201802-0304OC

@article{0a2b721567ca45a08629a08804381b96,

title = "Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10–pulmonary function association",

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 (FEV 1 , FVC, and FEV 1 /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 Results: DPA and DHA were positively associated with FEV 1 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 3 10 29 across discovery and replication cohorts). The rs11693320-A allele (frequency, z80%) was associated with lower FVC (P SNP = 2.1 3 10 29 ; b SNP = 2161.0 ml), and the association was attenuated by higher DHA levels (P SNP 3DHA interaction = 2.1 3 10 27 ; b SNP 3DHA 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 = "FEV, FVC, Genome-wide association study, Omega-3 fatty acids, Smoking",

author = "Jiayi Xu and Gaddis, {Nathan C.} and Bartz, {Traci M.} and Ruixue Hou and Manichaikul, {Ani W.} and Nathan Pankratz and Smith, {Albert V.} and Fangui Sun and Natalie Terzikhan and Markunas, {Christina A.} and Patchen, {Bonnie K.} and Matthew Schu and Beydoun, {May A.} and Brusselle, {Guy G.} and Gudny Eiriksdottir and Xia Zhou and Wood, {Alexis C.} and Mariaelisa Graff and Harris, {Tamara B.} and {Arfan Ikram}, M. and Jacobs, {David R.} and Launer, {Lenore J.} and Lemaitre, {Rozenn N.} and O{\textquoteright}Connor, {George T.} and Oelsner, {Elizabeth C.} and Psaty, {Bruce M.} and Vasan, {Ramachandran S.} and Rohde, {Rebecca R.} and Rich, {Stephen S.} and Rotter, {Jerome I.} and Sudha Seshadri and Smith, {Lewis J.} and Henning Tiemeier and Tsai, {Michael Y.} and Uitterlinden, {Andr{\'e} G.} and {Saroja Voruganti}, V. and Hanfei Xu and Zilh{\~a}o, {Nuno R.} and Myriam Fornage and {Carola Zillikens}, M. and London, {Stephanie J.} and {Graham Barr}, R. and Jos{\'e}e Dupuis and Gharib, {Sina A.} and Vilmundur Gudnason and Lies Lahousse and North, {Kari E.} and Steffen, {Lyn M.} and Cassano, {Patricia A.} and Hancock, {Dana B.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 by the American Thoracic Society.",

year = "2019",

month = mar,

day = "1",

doi = "10.1164/rccm.201802-0304OC",

language = "English (US)",

volume = "199",

pages = "631--642",

journal = "American journal of respiratory and critical care medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "5",

}

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, Arfan Ikram, M, 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, Saroja Voruganti, V, Xu, H, Zilhão, NR, Fornage, M, Carola Zillikens, M, London, SJ, Graham Barr, R, Dupuis, J, Gharib, SA, Gudnason, V, Lahousse, L, North, KE, Steffen, LM, Cassano, PA & Hancock, DB 2019, '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. https://doi.org/10.1164/rccm.201802-0304OC

TY - JOUR

T1 - Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10–pulmonary function association

AU - Xu, Jiayi

AU - Gaddis, Nathan C.

AU - Bartz, Traci M.

AU - Hou, Ruixue

AU - Manichaikul, Ani W.

AU - Pankratz, Nathan

AU - Smith, Albert V.

AU - Sun, Fangui

AU - Terzikhan, Natalie

AU - Markunas, Christina A.

AU - Patchen, Bonnie K.

AU - Schu, Matthew

AU - Beydoun, May A.

AU - Brusselle, Guy G.

AU - Eiriksdottir, Gudny

AU - Zhou, Xia

AU - Wood, Alexis C.

AU - Graff, Mariaelisa

AU - Harris, Tamara B.

AU - Arfan Ikram, M.

AU - Jacobs, David R.

AU - Launer, Lenore J.

AU - Lemaitre, Rozenn N.

AU - O’Connor, George T.

AU - Oelsner, Elizabeth C.

AU - Psaty, Bruce M.

AU - Vasan, Ramachandran S.

AU - Rohde, Rebecca R.

AU - Rich, Stephen S.

AU - Rotter, Jerome I.

AU - Seshadri, Sudha

AU - Smith, Lewis J.

AU - Tiemeier, Henning

AU - Tsai, Michael Y.

AU - Uitterlinden, André G.

AU - Saroja Voruganti, V.

AU - Xu, Hanfei

AU - Zilhão, Nuno R.

AU - Fornage, Myriam

AU - Carola Zillikens, M.

AU - London, Stephanie J.

AU - Graham Barr, R.

AU - Dupuis, Josée

AU - Gharib, Sina A.

AU - Gudnason, Vilmundur

AU - Lahousse, Lies

AU - North, Kari E.

AU - Steffen, Lyn M.

AU - Cassano, Patricia A.

AU - Hancock, Dana B.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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 (FEV 1 , FVC, and FEV 1 /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 Results: DPA and DHA were positively associated with FEV 1 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 3 10 29 across discovery and replication cohorts). The rs11693320-A allele (frequency, z80%) was associated with lower FVC (P SNP = 2.1 3 10 29 ; b SNP = 2161.0 ml), and the association was attenuated by higher DHA levels (P SNP 3DHA interaction = 2.1 3 10 27 ; b SNP 3DHA 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.

AB - 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 (FEV 1 , FVC, and FEV 1 /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 Results: DPA and DHA were positively associated with FEV 1 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 3 10 29 across discovery and replication cohorts). The rs11693320-A allele (frequency, z80%) was associated with lower FVC (P SNP = 2.1 3 10 29 ; b SNP = 2161.0 ml), and the association was attenuated by higher DHA levels (P SNP 3DHA interaction = 2.1 3 10 27 ; b SNP 3DHA 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.

KW - FEV

KW - FVC

KW - Genome-wide association study

KW - Omega-3 fatty acids

KW - Smoking

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UR - http://www.scopus.com/inward/citedby.url?scp=85062241060&partnerID=8YFLogxK

U2 - 10.1164/rccm.201802-0304OC

DO - 10.1164/rccm.201802-0304OC

M3 - Article

C2 - 30199657

AN - SCOPUS:85062241060

SN - 1073-449X

VL - 199

SP - 631

EP - 642

JO - American journal of respiratory and critical care medicine

JF - American journal of respiratory and critical care medicine

IS - 5

ER -

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

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