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This study aims to investigate the interrelationships of vitamin D deficiency, biomarkers of SIR, and mortality. We used multivariate logistic regression with adjustment for 51 covariates to assess the associations of vitamin D deficiency with disadvantageous levels of nine biomarkers of SIR in the UK Biobank cohort. Furthermore, we tested with Cox regression and mediation analysis whether biomarkers of SIR and vitamin D deficiency were independently associated with mortality. We included 397,737 participants aged 37\u201373\u00a0years. Vitamin D deficiency was associated with disadvantageous levels of all blood cell count-based biomarkers, but not with C-reactive protein (CRP)-based biomarkers after adjustment for body weight. Vitamin D deficiency and all biomarkers of SIR were significantly associated with all-cause mortality and mortality from cancer, cardiovascular and respiratory disease. The strength of these associations was unaltered if vitamin D deficiency and biomarkers of SIR were put in the same model. This finding was further supported by the mediation analyses. This study showed that vitamin D deficiency is associated with disadvantageous levels of blood cell count-based but not CRP-based biomarkers of SIR. Vitamin D deficiency and systemic inflammation were independently and strongly associated with mortality. The potential of clinical interventions against both vitamin D deficiency and underlying causes of systemic inflammation should be explored.<\/jats:p>","DOI":"10.1007\/s10654-023-01023-2","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T02:01:25Z","timestamp":1687312885000},"page":"957-971","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["About the associations of vitamin D deficiency and biomarkers of systemic inflammatory response with all-cause and cause-specific mortality in a general population sample of almost 400,000 UK Biobank participants"],"prefix":"10.1007","volume":"38","author":[{"given":"Sha","family":"Sha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tafirenyika","family":"Gwenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ju","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-4521","authenticated-orcid":false,"given":"Ben","family":"Sch\u00f6ttker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"issue":"11","key":"1023_CR1","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1038\/s41430-020-0558-y","volume":"74","author":"K Amrein","year":"2020","unstructured":"Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, K\u00f6stenberger M, Tmava Berisha A, et al. 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