Evidence map›Paper›PMID 25411281›Full record

SynthesisThe American journal of clinical nutrition2014

Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations.

Hassan S Dashti, M Kyla Shea, Caren E Smith, Toshiko Tanaka, Adela Hruby, Kris Richardson, Thomas J Wang, Mike A Nalls, Xiuqing Guo, Yongmei Liu and 8 more

2 registry-linked trialsOpen access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The American journal of clinical nutrition, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00005121 completednot on this map

Framingham Heart Study

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran1948 to 2008ConditionsCardiovascular Diseases, Heart Diseases, Coronary Disease, Cerebrovascular Accident
NCT00005487 active not recruitingnot on this map

Multi-Ethnic Study of Atherosclerosis (MESA)

TypeobservationalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran1999 to 2030Enrolled6,418ConditionsAtherosclerosis, Cardiovascular Diseases, Heart Diseases, Coronary Artery Disease
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 2 countries.

Hassan S DashtiFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
M Kyla SheaFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Caren E SmithFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Toshiko TanakaFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Adela HrubyFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Kris RichardsonFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Thomas J WangFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Mike A NallsFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Xiuqing GuoFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Yongmei LiuFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Jie YaoFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Dalin LiFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
W Craig JohnsonFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Emelia J BenjaminFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Stephen B KritchevskyFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
David S SiscovickFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
José M OrdovásFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Sarah L BoothFrom the Nutrition and Genomics Laboratory (HSD, CES, KR, and JMO), Vitamin K Laboratory (MKS and SLB), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA; the Translational Gerontology Branch (TT), Laboratory of Neurogenetics (MAN), National Institute on Aging, Baltimore, MD; the Department of Nutrition, Harvard School of Public Health, Boston, MA (AH); the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (TJW); the Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (XG and JY); the Department of Public Health Sciences (YL), Sticht Center on Aging (SBK), Wake Forest Medical Center, Winston-Salem, NC; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (DL); the Department of Biostatistics, University of Washington, Seattle, WA (WCJ); Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA (EJB); the Department of Medicine, Boston University School of Medicine, Boston, MA (EJB); New York Academy of Medicine, New York, NY (DSS); the Department of Epidemiology, Centro Nacional Investigaciones Cardiovasculares (CNIC), Madrid, Spain (JMO); and Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain (JMO). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.
Tufts University · USJean Mayer Human Nutrition Research Center on Aging · USCedars-Sinai Medical Center · USNational Institutes of Health · USHarvard University Press · USNew York Academy of Medicine · USUniversity of California, Los Angeles · USUniversity of Washington · US

Funding

Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
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6 · The paper itself

Abstract

backgroundPoor vitamin K status is linked to greater risk of several chronic diseases. Age, sex, and diet are determinants of circulating vitamin K; however, there is still large unexplained interindividual variability in vitamin K status. Although a strong genetic component has been hypothesized, this has yet to be examined by a genome-wide association (GWA) study.

objectiveThe objective was to identify common genetic variants associated with concentrations of circulating phylloquinone, the primary circulating form of vitamin K.

designWe conducted a 2-stage GWA meta-analysis of circulating phylloquinone in 2 populations of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Nutrition Working Group. Circulating phylloquinone was measured by using reversed-phase high-performance liquid chromatography. Results from adjusted cohort-specific discovery GWA analyses were meta-analyzed with inverse variance weights (n = 2138). Associations with circulating phylloquinone at P < 1 × 10(-6) were then evaluated in a second-stage analysis consisting of one independent cohort (n = 265).

resultsNo significant association was observed for circulating phylloquinone at the genome-wide significance level of 5 × 10(-8). However, from the discovery GWA, there were 11 single-nucleotide polymorphism (SNP) associations with circulating phylloquinone at P < 1 × 10(-6), including a functional variant previously associated with warfarin dose and altered phylloquinone metabolism. These SNPs are on 5 independent loci on 11q23.3, 8q24.3, 5q22.3, 2p12, and 19p13.12, and they fall within or near the candidate genes APOA1/C3/A4/A5 cluster (involved in lipoprotein metabolism), COL22A1, CDO1, CTNAA2, and CYP4F2 (a phylloquinone oxidase), respectively. Second-stage analysis in an independent cohort further suggests the association of the 5q22.3 locus with circulating phylloquinone (P < 0.05).

conclusionsMultiple candidate genes related to lipoprotein and vitamin K metabolism were identified as potential determinants of circulating phylloquinone. Further investigation with a larger sample is warranted to verify our initial findings and identify other loci contributing to circulating phylloquinone. Trials related to this study were registered at clinicaltrials.gov as NCT00005121 (Framingham Offspring Study) and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Indexed as

Genome-Wide Association StudyPolymorphism, Single NucleotideChromatography, LiquidEnergy IntakeGenetic LociGenotyping TechniquesHumansLipoproteinsMultigene FamilyObservational Studies as TopicVitamin K 1White PeopleLipoproteinsVitamin K 1CYP4F2geneticsGWASphylloquinonevitamin K

Identifiers

PMID25411281
PMCPMC4232014
OpenAlexW2114609901

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.