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Am J Respir Crit Care Med. 2019 Mar 1;199(5):631-642. doi: 10.1164/rccm.201802-0304OC.

Omega-3 Fatty Acids and Genome-Wide Interaction Analyses Reveal DPP10-Pulmonary Function Association.

Author information

1
1 Division of Nutritional Sciences, Cornell University, Ithaca, New York.
2
2 Research Computing Division.
3
3 Department of Biostatistics.
4
4 Cardiovascular Health Research Unit.
5
5 Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, North Carolina.
6
6 Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia.
7
7 Department of Laboratory Medicine and Pathology and.
8
8 Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
9
9 Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
10
10 Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
11
11 Department of Epidemiology.
12
12 Center for Omics Discovery and Epidemiology, Behavioral Health Research Division, and.
13
13 Genomics in Public Health and Medicine Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina.
14
14 Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
15
15 Department of Respiratory Medicine.
16
16 Icelandic Heart Association, Kopavogur, Iceland.
17
17 Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota.
18
18 USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
19
19 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
20
20 Department of Medicine.
21
21 The Pulmonary Center, Department of Medicine.
22
22 Department of Medicine, Columbia University, New York, New York.
23
23 Department of Epidemiology.
24
24 Department of Health Services, and.
25
25 Kaiser Permanente Washington Health Research Institute, Seattle, Washington.
26
26 Division of Cardiology and Preventive Medicine, Department of Medicine, and.
27
27 Boston University's and NHLBI's Framingham Heart Study, Framingham, Massachusetts.
28
28 Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California.
29
30 Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
30
29 Glenn Biggs Institute of Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas.
31
31 Division of Pulmonary and Critical Care, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
32
32 Department of Psychiatry.
33
33 Department of Child and Adolescent Psychiatry, and.
34
34 Institute of Molecular Medicine and.
35
35 Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas.
36
37 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
37
36 Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Leiden, the Netherlands.
38
38 Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina.
39
39 Center for Lung Biology, University of Washington, Seattle, Washington.
40
40 University of Iceland, Reykjavik, Iceland.
41
41 Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
42
42 Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, New York.

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 (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.

RESULTS:

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).

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

PMID:
30199657
PMCID:
PMC6396866
[Available on 2020-03-01]
DOI:
10.1164/rccm.201802-0304OC

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