The authors thank Professor James Booth in the Department of Biological Statistics and Computational Biology at Cornell University for providing advice on meta-analysis. The authors thank the staff (Lynn Johnson and Francoise Vermeylen) in Cornell Statistical Consulting Unit for their role in providing advice on methods. The authors also thank Hanfei Xu, PhD student in the research group of Dr Josée Dupuis for his assistance on residual model testing in the Framingham Heart Study.
This work was supported by National Institutes of Health (NIH) grant no. R21 HL125574 funded by the National Heart, Lung, and Blood Institute (NHLBI) and the NIH Office of Dietary Supplements (ODS) (multiple principal investigators (MPIs): D. B. H. and P. A. C.). The corresponding author (P. A. C.) had full access to the data for the meta-analysis, and had final responsibility for the decision to submit for publication. No funding source had any role in the analysis of the data, the writing of the manuscript or the decision to submit it. This work was also supported in part by R01HL077612 (PI: R. G. B.) and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZO1 ES043012, PI: S. J. L.). S. J. L. is supported by the Intramural Research Program of NIH, National Institute of Environmental Health Sciences. Infrastructure for the CHARGE Consortium is supported in part by the NHLBI grant R01HL105756. The Age, Gene, Environment, Susceptibility (AGES)–Reykjavik Study has been funded by NIH contracts N01-AG-1-2100 and 271201200022C, the National Institute on Aging (NIA) Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NHLBI contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C. 25(OH)D measurements were conducted with the support of R01 HL103706 from the NHLBI and R01 HL103706-S1 from the NIH ODS. The authors thank the staff and participants of the ARIC study for their important contributions. This Cardiovascular Health Study (CHS) research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086 and NHLBI grants U01HL080295, R01HL085251, R01HL087652, R01HL105756, R01HL103612, R01HL120393 and R01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through R01AG023629 from NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Vitamin D measurements were made possible by NHLBI (R01HL084443-01A2). This work in Framingham Heart Study was supported by NHLBI’s Framingham Heart Study contract (N01-HC-25195 and HHSN268201500001I). Vitamin D measurements in the Framingham study were made possible by NIA (R01 AG14759 to S. L. B.). The Health Aging and Body Composition cohort study was supported by NIA contracts N01AG62101, N01AG2103 and N01AG62106, NIA grant R01-AG028050, National Institute of Nursing Research grant R01-NR012459, and in part by the Intramural Research Program of the NIA, NIH. This research was further supported by RC1AG035835 and the serum vitamin D assays were supported by R01AG029364. The Multi-Ethnic Study of Atherosclerosis (MESA) study is conducted and supported by NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from NHLBI, UL1-TR-000040, UL1-TR-001079 and UL1-TR-001881 from the National Center for Research Resources and DK063491 from the National Institute of Diabetes and Digestive and Kidney Diseases. The MESA Lung study was supported by grants R01 HL077612, RC1 HL100543 and R01 HL093081 from NHLBI. Support for the Mineral Metabolite dataset was provided by grant HL096875. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands; the Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Dutch Ministry of Education, Culture, and Science; the Dutch Ministry for Health, Welfare, and Sports; the European Commission (DG XII), and the Municipality of Rotterdam. L. L. was a postdoctoral fellow of the Research Foundation—Flanders (FWO) in Brussels, Belgium. Part of this work was supported by a FWO-grant G035014N. DSM Nutritional Products AG, Kaiseraugst, Switzerland, sponsored the Vitamin D serum analyses. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C and HHSN268200900041C from the NHLBI, the Intramural Research Program of the NIA and an intra-agency agreement between NIA and NHLBI (AG0005).
P. A. C., D. B. H. and J. X. conceived and designed the study. R. G. B., J. L., J. D., S. A. G., L. L., S. J. L., K. E. N., A. V. S., B. M. P. and L. M. S. provided the data and supervised the data analysis in each cohort. J. X., T. M. B., R. R. R., A. V. S., A. W. M., F. S., N. T. and X. Z. analysed data within each cohort. J. X., P. A. C. and D. B. H. meta-analysed and interpreted the data, co-wrote and edited the first draft of the manuscript and had primary responsibility for final content. All authors provided data, analytic support and/or study design suggestions at all stages, critically reviewed the manuscript and read and approved the final version.
Dr B. M. P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. All other authors have no conflicts of interest. There is no commercial support or financial interest from the tobacco industry for the research presented.
The study sponsors were not involved in study design, data collection, data analysis, data interpretation, report writing or decisions to submit the paper for publication. P. A. C. and D. B. H. had final responsibility for the decision to submit for publication.
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