PMID- 29738550
OWN - NLM
STAT- MEDLINE
DCOM- 20180801
LR  - 20240116
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 5
DP  - 2018
TI  - Genome-wide association meta-analysis of circulating odd-numbered chain saturated 
      fatty acids: Results from the CHARGE Consortium.
PG  - e0196951
LID - 10.1371/journal.pone.0196951 [doi]
LID - e0196951
AB  - BACKGROUND: Odd-numbered chain saturated fatty acids (OCSFA) have been associated 
      with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are 
      found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are 
      relatively unknown, and the influence of non-dietary determinants, including 
      genetic factors, on circulating levels of OCSFA is not established. OBJECTIVE: To 
      elucidate the biological processes that influence circulating levels of OCSFA by 
      investigating associations between genetic variation and OCSFA. DESIGN: We 
      performed a meta-analysis of genome-wide association studies (GWAS) of plasma 
      phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 
      individuals of European descent. We also investigated relationships between 
      specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, 
      associated with adult-onset lactase intolerance, with circulating levels of 
      dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes 
      with C23:0 levels. RESULTS: We found no genome-wide significant evidence that 
      common genetic variation is associated with circulating levels of C15:0 or C23:0. 
      In two cohorts with available data, we identified one intronic SNP (rs13361131) 
      in myosin X gene (MYO10) associated with C17:0 level (P = 1.37x10-8), and two 
      intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 
      (DLEU1) region associated with C19:0 level (P = 7.07x10-9). In contrast, when 
      using a candidate-gene approach, we found evidence that three SNPs in LCT 
      (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 
      level (adjusted P = 4x10-2). In addition, nine SNPs in the ceramide synthase 4 
      (CERS4) region were associated with circulating C23:0 levels (adjusted P<5x10-2). 
      CONCLUSIONS: Our findings suggest that circulating levels of OCSFA may be 
      predominantly influenced by non-genetic factors. SNPs associated with C17:0 level 
      in the LCT gene may reflect genetic influence in dairy consumption or in 
      metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of 
      genetic factors in the synthesis of sphingomyelin.
FAU - de Oliveira Otto, Marcia C
AU  - de Oliveira Otto MC
AUID- ORCID: 0000-0002-4585-0688
AD  - Division of Epidemiology, Human Genetics and Environmental Sciences, the 
      University of Texas Health Science Center, School of Public Health, Houston, TX, 
      United States of America.
FAU - Lemaitre, Rozenn N
AU  - Lemaitre RN
AD  - Cardiovascular Health Research Unit, Department of Medicine, University of 
      Washington, Seattle, WA, United States of America.
FAU - Sun, Qi
AU  - Sun Q
AD  - Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public 
      Health and Channing Division of Network Medicine, and Harvard Medical School, 
      Boston, MA, United States of America.
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United 
      States of America.
FAU - King, Irena B
AU  - King IB
AD  - University of New Mexico, Albuquerque, NM, United States of America.
FAU - Wu, Jason H Y
AU  - Wu JHY
AD  - The George Institute for Global Health and the Faculty of Medicine, University of 
      New South Wales, Sydney, Australia.
FAU - Manichaikul, Ani
AU  - Manichaikul A
AD  - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 
      United States of America.
FAU - Rich, Stephen S
AU  - Rich SS
AD  - Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 
      United States of America.
FAU - Tsai, Michael Y
AU  - Tsai MY
AD  - Department of Laboratory Medicine and Pathology, University of Minnesota, 
      Minneapolis, MN, United States of America.
FAU - Chen, Y D
AU  - Chen YD
AD  - Institute for Translational Genomics and Population Sciences, Los Angeles 
      Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, 
      United States of America.
FAU - Fornage, Myriam
AU  - Fornage M
AD  - Key Laboratory of Nutrition and Metabolism, the University of Texas Health 
      Science Center, School of Public Health, Houston, TX, United States of America.
FAU - Weihua, Guan
AU  - Weihua G
AD  - Department of Biostatistics, University of Minnesota, Minneapolis, MN, United 
      States of America.
FAU - Aslibekyan, Stella
AU  - Aslibekyan S
AD  - College of Public Health, University of Kentucky, Lexington, KY, United States of 
      America.
FAU - Irvin, Marguerite R
AU  - Irvin MR
AD  - College of Public Health, University of Kentucky, Lexington, KY, United States of 
      America.
FAU - Kabagambe, Edmond K
AU  - Kabagambe EK
AD  - College of Public Health, University of Kentucky, Lexington, KY, United States of 
      America.
FAU - Arnett, Donna K
AU  - Arnett DK
AD  - College of Public Health, University of Kentucky, Lexington, KY, United States of 
      America.
FAU - Jensen, Majken K
AU  - Jensen MK
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United 
      States of America.
AD  - Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public 
      Health, Boston MA, United States of America.
FAU - McKnight, Barbara
AU  - McKnight B
AD  - Department of Biostatistics, University of Washington, Seattle, WA, United States 
      of America.
FAU - Psaty, Bruce M
AU  - Psaty BM
AD  - Cardiovascular Health Research Unit, Department of Medicine, University of 
      Washington, Seattle, WA, United States of America.
AD  - Kaiser Permanente Washington Health Research Institute, Seattle, WA, United 
      States of America.
FAU - Steffen, Lyn M
AU  - Steffen LM
AD  - School of Public Health, Division of Epidemiology and Community Health, 
      University of Minnesota, Minneapolis, Minnesota, United States of America.
FAU - Smith, Caren E
AU  - Smith CE
AD  - Nutrition and Genomics Laboratory, Jean Mayer USDA HNRCA at Tufts University, 
      Boston, MA, United States of America.
FAU - Riserus, Ulf
AU  - Riserus U
AD  - Department of Public Health and Caring Sciences, Uppsala University, Uppsala, 
      Sweden.
FAU - Lind, Lars
AU  - Lind L
AD  - Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
FAU - Hu, Frank B
AU  - Hu FB
AD  - Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public 
      Health and Channing Division of Network Medicine, and Harvard Medical School, 
      Boston, MA, United States of America.
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United 
      States of America.
FAU - Rimm, Eric B
AU  - Rimm EB
AD  - Department of Nutrition and Epidemiology, Harvard T.H. Chan School of Public 
      Health and Channing Division of Network Medicine, and Harvard Medical School, 
      Boston, MA, United States of America.
AD  - Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United 
      States of America.
FAU - Siscovick, David S
AU  - Siscovick DS
AD  - The New York Academy of Medicine, New York, NY, United States of America.
FAU - Mozaffarian, Dariush
AU  - Mozaffarian D
AD  - Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, 
      United States of America.
LA  - eng
GR  - R01 HL120393/HL/NHLBI NIH HHS/United States
GR  - U01 HL130114/HL/NHLBI NIH HHS/United States
GR  - U01 HL120393/HL/NHLBI NIH HHS/United States
GR  - U01-HL072524/NH/NIH HHS/United States
GR  - R00-HL098459/NH/NIH HHS/United States
GR  - R01HL130735/NH/NIH HHS/United States
GR  - K08 HL112845/HL/NHLBI NIH HHS/United States
GR  - R01 HL130735/HL/NHLBI NIH HHS/United States
GR  - HHSN268201300025C/AG/NIA NIH HHS/United States
GR  - HHSN268201300026C/HL/NHLBI NIH HHS/United States
GR  - K01 HL136700/HL/NHLBI NIH HHS/United States
GR  - R01 HL085710/HL/NHLBI NIH HHS/United States
GR  - R01HL085710/NH/NIH HHS/United States
GR  - R00 HL098459/HL/NHLBI NIH HHS/United States
GR  - CA186107/NH/NIH HHS/United States
GR  - N02HL64278/HL/NHLBI NIH HHS/United States
GR  - 3R01HL085710-07S1/NH/NIH HHS/United States
GR  - R01 HL105756/HL/NHLBI NIH HHS/United States
GR  - HL105756/NH/NIH HHS/United States
GR  - HL136700/NH/NIH HHS/United States
GR  - R01HL135920/NH/NIH HHS/United States
GR  - U01 HG004729/HG/NHGRI NIH HHS/United States
GR  - N02-HL-64278/NH/NIH HHS/United States
GR  - U01 HL072524/HL/NHLBI NIH HHS/United States
GR  - U01-HG004729/NH/NIH HHS/United States
GR  - R01 HL135920/HL/NHLBI NIH HHS/United States
GR  - K08 HL112845/NH/NIH HHS/United States
GR  - UM1 CA186107/CA/NCI NIH HHS/United States
GR  - R01 HL115189/HL/NHLBI NIH HHS/United States
GR  - R01HL115189/NH/NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20180508
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DLEU1 lncRNA, human)
RN  - 0 (Fatty Acids)
RN  - 0 (MYO10 protein, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Sphingomyelins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.3.1.24 (CERS4 protein, human)
RN  - EC 2.3.1.24 (Sphingosine N-Acyltransferase)
RN  - EC 3.2.1.108 (Lactase)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Fatty Acids/blood/*genetics
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Introns/genetics
MH  - Lactase/genetics
MH  - Myosins/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Long Noncoding
MH  - Sphingomyelins/biosynthesis/genetics
MH  - Sphingosine N-Acyltransferase/*genetics
MH  - Tumor Suppressor Proteins/*genetics
PMC - PMC5940220
COIS- Competing Interests: Dr. Mozaffarian reports ad hoc honoraria or consulting from 
      Life Sciences Research Organization, Astra Zeneca, Boston Heart Diagnostics, 
      GOED, DSM, Nutrition Impact, Haas Avocado Board, and Pollock Communications; 
      scientific advisory board, Omada Health and Elysium Health; and chapter royalties 
      from UpToDate. Dr. Psaty serves on the DSMB of a clinical trial funded by Zoll 
      LifeCor and on the Steering Committee of the Yale Open Data Access Project funded 
      by Johnson & Johnson. The other authors reported no conflict of interest.
EDAT- 2018/05/09 06:00
MHDA- 2018/08/02 06:00
PMCR- 2018/05/08
CRDT- 2018/05/09 06:00
PHST- 2018/02/14 00:00 [received]
PHST- 2018/04/23 00:00 [accepted]
PHST- 2018/05/09 06:00 [entrez]
PHST- 2018/05/09 06:00 [pubmed]
PHST- 2018/08/02 06:00 [medline]
PHST- 2018/05/08 00:00 [pmc-release]
AID - PONE-D-18-05019 [pii]
AID - 10.1371/journal.pone.0196951 [doi]
PST - epublish
SO  - PLoS One. 2018 May 8;13(5):e0196951. doi: 10.1371/journal.pone.0196951. 
      eCollection 2018.