TY - JOUR AU - Hu F. AU - Chasman D. AU - Ridker P. AU - Arnett D. AU - Fornage M. AU - Wu J. AU - Psaty B. AU - Wang L. AU - Mozaffarian D. AU - Chu A. AU - Siscovick D. AU - Lemaitre R. AU - King I. AU - Ma Y. AU - Djousse L. AU - Tanaka T. AU - Smith C. AU - Follis J. AU - Nettleton J. AU - Foy M. AU - Manichakul A. AU - Wu H. AU - Steffen L. AU - Kabagambe E. AU - Ferruci L. AU - Chen Y. AU - Rich S. AU - Tang W. AU - McKnight B. AU - Tsai M. AU - Bandinelli S. AU - Rotter J. AU - Sun Q. AU - Lumley T. AU - Chiuve S. AU - Ordovas J. AB -

SCOPE: 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. METHODS AND 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. CONCLUSION: 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.

AD - Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA*
Department of Mathematics, Computer Science, and Cooperative Engineering, University of St. Thomas, Houston, TX, USA.
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.
The George Institute for Global Health, The University of Sydney, Sydney, NSW, Australia.
Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA, USA.
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
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.
Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA.
Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Boston Veterans Affairs Healthcare System, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Biostatistics, University of Washington, Seattle, WA, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Florence, Italy.
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.
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.
Department of Epidemiology, Section on Statistical Genetics, and The Office of Energetics, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Internal Medicine, Division of Endocrinology, University of New Mexico, Albuquerque, NM, USA.
Department of Statistics, University of Auckland, Auckland, New Zealand.
Department of Epidemiology and Population Genetics, Centro Nacional Investigacion Cardiovasculares (CNIC), Madrid, Spain.
Instituto Madrilenos de Estudios Avanzados Alimentacion, Madrid, Spain. AN - 25626431 BT - Molecular Nutrition and Food Research C2 - PMC4491005 C6 - Nihms668757 DP - NLM ET - 2015/01/30 LA - eng LB - AUS
FP M1 - 7 N1 - Smith, Caren E
Follis, Jack L
Nettleton, Jennifer A
Foy, Millennia
Wu, Jason H Y
Ma, Yiyi
Tanaka, Toshiko
Manichakul, Ani W
Wu, Hongyu
Chu, Audrey Y
Steffen, Lyn M
Fornage, Myriam
Mozaffarian, Dariush
Kabagambe, Edmond K
Ferruci, Luigi
Chen, Yii-Der Ida
Rich, Stephen S
Djousse, Luc
Ridker, Paul M
Tang, Weihong
McKnight, Barbara
Tsai, Michael Y
Bandinelli, Stefania
Rotter, Jerome I
Hu, Frank B
Chasman, Daniel I
Psaty, Bruce M
Arnett, Donna K
King, Irena B
Sun, Qi
Wang, Lu
Lumley, Thomas
Chiuve, Stephanie E
Siscovick, David S
Ordovas, Jose M
Lemaitre, Rozenn N
AG023629/AG/NIA NIH HHS/United States
CA047988/CA/NCI NIH HHS/United States
CA055075/CA/NCI NIH HHS/United States
DK063491/DK/NIDDK NIH HHS/United States
HHSN268200800007C/PHS HHS/United States
HHSN268200900041C/PHS HHS/United States
HHSN268201100005C/PHS HHS/United States
HHSN268201100006C/PHS HHS/United States
HHSN268201100007C/PHS HHS/United States
HHSN268201100008C/PHS HHS/United States
HHSN268201100009C/PHS HHS/United States
HHSN268201100010C/PHS HHS/United States
HHSN268201100011C/PHS HHS/United States
HHSN268201100012C/PHS HHS/United States
HHSN268201200036C/PHS HHS/United States
HHSN268201300025C/PHS HHS/United States
HHSN268201300026C/PHS HHS/United States
HHSN268201300027C/PHS HHS/United States
HHSN268201300028C/PHS HHS/United States
HHSN268201300029C/PHS HHS/United States
HL043851/HL/NHLBI NIH HHS/United States
HL078885/HL/NHLBI NIH HHS/United States
HL080295/HL/NHLBI NIH HHS/United States
HL080467/HL/NHLBI NIH HHS/United States
HL085710/HL/NHLBI NIH HHS/United States
HL087652/HL/NHLBI NIH HHS/United States
HL099355/HL/NHLBI NIH HHS/United States
HL105756/HL/NHLBI NIH HHS/United States
HL54776/HL/NHLBI NIH HHS/United States
HL60712/HL/NHLBI NIH HHS/United States
HSN268200625226C/PHS HHS/United States
K08 HL112845/HL/NHLBI NIH HHS/United States
N01-HC-95159/HC/NHLBI NIH HHS/United States
N01-HC-95160/HC/NHLBI NIH HHS/United States
N01-HC-95161/HC/NHLBI NIH HHS/United States
N01-HC-95162/HC/NHLBI NIH HHS/United States
N01-HC-95163/HC/NHLBI NIH HHS/United States
N01-HC-95164/HC/NHLBI NIH HHS/United States
N01-HC-95165/HC/NHLBI NIH HHS/United States
N01-HC-95166/HC/NHLBI NIH HHS/United States
N01-HC-95167/HC/NHLBI NIH HHS/United States
N01-HC-95168/HC/NHLBI NIH HHS/United States
N01-HC-95169/HC/NHLBI NIH HHS/United States
N01HC55222/HC/NHLBI NIH HHS/United States
N01HC85079/HC/NHLBI NIH HHS/United States
N01HC85080/HC/NHLBI NIH HHS/United States
N01HC85081/HC/NHLBI NIH HHS/United States
N01HC85082/HC/NHLBI NIH HHS/United States
N01HC85083/HC/NHLBI NIH HHS/United States
N01HC85086/HC/NHLBI NIH HHS/United States
N02HL64278/HL/NHLBI NIH HHS/United States
P01 CA87969/CA/NCI NIH HHS/United States
R00 HL097068/HL/NHLBI NIH HHS/United States
R00-HL095649/HL/NHLBI NIH HHS/United States
R00HL098459/HL/NHLBI NIH HHS/United States
R01 HL034594/HL/NHLBI NIH HHS/United States
R01 HL085710/HL/NHLBI NIH HHS/United States
R01 HL091357/HL/NHLBI NIH HHS/United States
R01 HL35464/HL/NHLBI NIH HHS/United States
R01-HL-084099/HL/NHLBI NIH HHS/United States
R01HL086694/HL/NHLBI NIH HHS/United States
R01HL087641/HL/NHLBI NIH HHS/United States
R01HL59367/HL/NHLBI NIH HHS/United States
RR-024156/RR/NCRR NIH HHS/United States
U01-HG-004424/HG/NHGRI NIH HHS/United States
U01-HG-004446/HG/NHGRI NIH HHS/United States
U01-HG-004729/HG/NHGRI NIH HHS/United States
U01HG004402/HG/NHGRI NIH HHS/United States
U01HL072524/HL/NHLBI NIH HHS/United States
UL1 TR000124/TR/NCATS NIH HHS/United States
UL1RR025005/RR/NCRR NIH HHS/United States
UL1TR000124/TR/NCATS NIH HHS/United States
UM1 CA167552/CA/NCI NIH HHS/United States
Intramural NIH HHS/United States
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Germany
Mol Nutr Food Res. 2015 Jul;59(7):1373-83. doi: 10.1002/mnfr.201400734. Epub 2015 Mar 16. N2 -

SCOPE: 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. METHODS AND 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. CONCLUSION: 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.

PY - 2015 SN - 1613-4133 (Electronic)
1613-4125 (Linking) SP - 1373 EP - 83 T2 - Molecular Nutrition and Food Research TI - 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 VL - 59 Y2 - FY16 ER -