title: Dietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: Meta-analysis of nine studies in the CHARGE consortium.
abstract: METHODS
  Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid.
  
  
  RESULTS
  We conducted meta-analyses (N = 11 668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid.
  
  
  CONCLUSIONS
  Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes.
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA*
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Department of Mathematics, Computer Science, and Cooperative Engineering, University of St. Thomas, Houston, TX, USA.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Follis
authors.affiliation: Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Nettleton
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Millennia
authors.initials: M
authors.lastname: Foy
authors.affiliation: The George Institute for Global Health, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Jason H Y
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA*
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.|Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ani W
authors.initials: AW
authors.lastname: Manichakul
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Audrey Y
authors.initials: AY
authors.lastname: Chu
authors.affiliation: Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
authors.forename: Lyn M
authors.initials: LM
authors.lastname: Steffen
authors.affiliation: Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.|Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Harvard Medical School, Boston, MA, USA.|Department of Nutrition, Harvard School of Public Health, Harvard Medical School, Boston, MA, USA.|Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferruci
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA.
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.|Boston Veterans Affairs Healthcare System, Boston, MA, USA.
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.affiliation: Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Florence, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.|Harvard School of Public Health, Boston, MA, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.|Department of Epidemiology, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.|Department of Health Services, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Epidemiology, Section on Statistical Genetics, and The Office of Energetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.|Harvard School of Public Health, Boston, MA, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Statistics, University of Auckland, Auckland, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Chiuve
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.|Department of Epidemiology, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA*|Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares (CNIC), Madrid, Spain.|Instituto Madrilenõs de Estudios Avanzados Alimentación, Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000217:Acyltransferases / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D002262:Carboxy-Lyases / Q000235:genetics*; D000090943:Delta-5 Fatty Acid Desaturase; D004032:Diet; D004281:Docosahexaenoic Acids / Q000097:blood; D015118:Eicosapentaenoic Acid / Q000097:blood; D004910:Erythrocyte Membrane / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics*; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000097:blood / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000090943:Delta-5 Fatty Acid Desaturase; C000630967:ELOVL2 protein, human; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; C485100:GCKR protein, human; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; D000217:Acyltransferases; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; C018764:2-acylglycerophosphate acyltransferase; D002262:Carboxy-Lyases; C000606985:PDXDC1 protein, human
keywords: FADS1; Gene-diet interactions; Meta-analysis; Omega-3 fatty acids