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 D 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 & 30 others David R Jacobs Jr, 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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)631-642
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Volume199
Issue number5
DOIs
StatePublished - Mar 1 2019

Fingerprint

Omega-3 Fatty Acids
Genome
Single Nucleotide Polymorphism
Docosahexaenoic Acids
Respiratory Function Tests
Meta-Analysis
Lung
alpha-Linolenic Acid
Eicosapentaenoic Acid
Genetic Predisposition to Disease
Unsaturated Fatty Acids
Gene Frequency
Epidemiology
Anti-Inflammatory Agents
Biomarkers
Smoking
Health
Research

Keywords

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

Cite this

Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10–pulmonary function association. / Xu, Jiayi; Gaddis, Nathan C.; Bartz, Traci M.; Hou, Ruixue; Manichaikul, Ani W.; Pankratz, Nathan D; Smith, Albert V.; Sun, Fangui; Terzikhan, Natalie; Markunas, Christina A.; Patchen, Bonnie K.; Schu, Matthew; Beydoun, May A.; Brusselle, Guy G.; Eiriksdottir, Gudny; Zhou, Xia; Wood, Alexis C.; Graff, Mariaelisa; Harris, Tamara B.; Arfan Ikram, M.; Jacobs Jr, David R; Launer, Lenore J.; Lemaitre, Rozenn N.; O’Connor, George T.; Oelsner, Elizabeth C.; Psaty, Bruce M.; Vasan, Ramachandran S.; Rohde, Rebecca R.; Rich, Stephen S.; Rotter, Jerome I.; Seshadri, Sudha; Smith, Lewis J.; Tiemeier, Henning; Tsai, Michael Y; Uitterlinden, André G.; Saroja Voruganti, V.; Xu, Hanfei; Zilhão, Nuno R.; Fornage, Myriam; Carola Zillikens, M.; London, Stephanie J.; Graham Barr, R.; Dupuis, Josée; Gharib, Sina A.; Gudnason, Vilmundur; Lahousse, Lies; North, Kari E.; Steffen, Lyn M; Cassano, Patricia A.; Hancock, Dana B.

In: American journal of respiratory and critical care medicine, Vol. 199, No. 5, 01.03.2019, p. 631-642.

Research output: Contribution to journalArticle

Xu, J, Gaddis, NC, Bartz, TM, Hou, R, Manichaikul, AW, Pankratz, ND, 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 Jr, 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
Xu, Jiayi ; Gaddis, Nathan C. ; Bartz, Traci M. ; Hou, Ruixue ; Manichaikul, Ani W. ; Pankratz, Nathan D ; Smith, Albert V. ; Sun, Fangui ; Terzikhan, Natalie ; Markunas, Christina A. ; Patchen, Bonnie K. ; Schu, Matthew ; Beydoun, May A. ; Brusselle, Guy G. ; Eiriksdottir, Gudny ; Zhou, Xia ; Wood, Alexis C. ; Graff, Mariaelisa ; Harris, Tamara B. ; Arfan Ikram, M. ; Jacobs Jr, David R ; Launer, Lenore J. ; Lemaitre, Rozenn N. ; O’Connor, George T. ; Oelsner, Elizabeth C. ; Psaty, Bruce M. ; Vasan, Ramachandran S. ; Rohde, Rebecca R. ; Rich, Stephen S. ; Rotter, Jerome I. ; Seshadri, Sudha ; Smith, Lewis J. ; Tiemeier, Henning ; Tsai, Michael Y ; Uitterlinden, André G. ; Saroja Voruganti, V. ; Xu, Hanfei ; Zilhão, Nuno R. ; Fornage, Myriam ; Carola Zillikens, M. ; London, Stephanie J. ; Graham Barr, R. ; Dupuis, Josée ; Gharib, Sina A. ; Gudnason, Vilmundur ; Lahousse, Lies ; North, Kari E. ; Steffen, Lyn M ; Cassano, Patricia A. ; Hancock, Dana B. / Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10–pulmonary function association. In: American journal of respiratory and critical care medicine. 2019 ; Vol. 199, No. 5. pp. 631-642.
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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 Pankratz, {Nathan D} 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 Jr}, {David R} and Launer, {Lenore J.} and Lemaitre, {Rozenn N.} and O’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.}",
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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 D

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 Jr, 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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