Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration.

While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.

Risk of Postpartum Dental Caries: Survival Analysis of Black/African American and White Women in Appalachia.

Background: Pregnancy is associated with increased risk of caries, but the extent this increase extends into the postpartum period is poorly understood. Study Objective: Describe the epidemiology of dental decay in the postpartum period among Black/African American and White American women and explore associations with potentially modifiable risk factors. Materials and Methods: We analyzed data from 1,131 Black/African American and White women participating in Center for Oral Health Research in Appalachia cohorts. Women were enrolled during the first two trimesters of pregnancy. Calibrated dental professionals completed dental examinations at the prenatal enrollment visit, and 2-month, 1-year, 2-year, and 3-year postpartum visits. Results: Between the prenatal visit and 2-month visit, the incidence of decayed, missing, and filled teeth (DMFT) increase was 6.92/100 person-months, compared to 3.6/100 person-months between the 2-month and 1-year visit. In a multivariate Cox proportional hazard regression predicting incidence of caries up to 3-years postpartum, being younger, having less than college education, a household income <$50,000, smoking cigarettes, a DMFT >0, a very poor or poor Oral hygiene Rating Index, lower salivary pH at enrollment, or frequently drinking 100% juice increased the hazard of new dental caries. Adjusting for race/ethnic group did not affect the direction or magnitude of observed associations. Conclusions: The strong associations of prior DMFT and Oral Rating Index with occurrence of new dental caries postpartum suggests that targeting young women for interventions to improve oral health may be more valuable for reducing caries incidence during pregnancy and in the postpartum period than targeting women only during pregnancy.

The mediating role of systemic inflammation and moderating role of racialization in disparities in incident dementia.

BACKGROUND: Exposure to systemic racism is linked to increased dementia burden. To assess systemic inflammation as a potential pathway linking exposure to racism and dementia disparities, we investigated the mediating role of C-reactive protein (CRP), a systemic inflammation marker, and the moderating role of the racialization process in incident dementia. METHODS: In the US Health and Retirement Study (n = 6,908), serum CRP was measured at baseline (2006, 2008 waves). Incident dementia was classified by cognitive tests over a six-year follow-up. Self-reported racialized categories were a proxy for exposure to the racialization process. We decomposed racialized disparities in dementia incidence (non-Hispanic Black and/or Hispanic vs. non-Hispanic white) into 1) the mediated effect of CRP, 2) the moderated portion attributable to the interaction between racialized group membership and CRP, and 3) the controlled direct effect (other pathways through which racism operates). RESULTS: The 6-year cumulative incidence of dementia is 12%. Among minoritized participants (i.e., non-Hispanic Black and/or Hispanic), high CRP levels ( ≥ 75th percentile or 4.73µg/mL) are associated with 1.26 (95%CI: 0.98, 1.62) times greater risk of incident dementia than low CRP ( < 4.73µg/mL). Decomposition analysis comparing minoritized versus non-Hispanic white participants shows that the mediating effect of CRP accounts for 3% (95% CI: 0%, 6%) of the racial disparity, while the interaction effect between minoritized group status and high CRP accounts for 14% (95% CI: 1%, 27%) of the disparity. Findings are robust to potential violations of causal mediation assumptions. CONCLUSIONS: Minoritized group membership modifies the relationship between systemic inflammation and incident dementia.

Higher levels of inflammation in blood are linked to greater dementia risk in older adults. Non-Hispanic Black and Hispanic Americans have higher inflammation levels compared to non-Hispanic white Americans. We conducted a study to examine whether high levels of inflammation could explain differences in dementia risk among these racial groups. We found that differences in inflammation levels in non-Hispanic Black or Hispanic adults modestly explain their higher risk of dementia compared to non-Hispanic white adults. These findings suggest that interventions aimed at reducing high levels of inflammation in minoritized US adults could ameliorate racial differences in dementia risk.