Background: Clefting of the lip with or without cleft palate (CLP) is the most common congenital craniofacial abnormality globally, affecting one in 700 live births. Traditional observational studies suggest an increased risk of adult depression among subjects with CLP, but these studies are subject to residual confounding.

Objective: We aimed to address residual confounding by evaluating the association between the genetically-predicted risk of CLP on the risk of adult depression in a Mendelian randomization framework.

Methods: We used single-nucleotide polymorphisms strongly associated (p-value <5e-6) with CLP as genetic instruments. Genetic associations with adult depression were extracted from separate studies. Three ancestry groups were evaluated: European, East Asian, and African. Two-sample Mendelian randomization inverse-variance weighted analyses were conducted, and sensitivity analyses using weighted median, weighted mode, and MR-Egger regression were performed to assess bias from genetic pleiotropy.

Results: The study included a total of 3,577 CLP cases and 10,345 controls, and 59,406 and 274,957 subjects with and without adult depression. Among subjects of African ancestry, a doubling of the genetically-predicted prevalence of CLP was associated with an odds ratio for adult depression of 1.28 (95% CI 0.94-1.75). Sensitivity analyses supported this finding. There was no clear association between CLP and adult depression in the European or East Asian ancestry groups.

Conclusion: This study suggests a causal association between cleft lip and risk of depression among subjects of African ancestry. Our findings warrant further investigation into the role of craniofacial malformations as a cause of depression, and an assessment of potential inequity.

Purpose: Chronic levels of inflammation are associated with higher risk of many chronic diseases. Physical activity (PA) levels lowers the risk of cancer, cardiovascular disease, diabetes and others. One mechanism for PA-induced protection may be through the immune system. We investigated the association between leisure-time PA and peripheral immune cell populations in a large representative national sample of the US general population.

Methods: 17,093 participants of the National Health and Nutrition Examination Survey 1999-2018 were included. Self-reported leisure-time PA was converted to metabolic equivalent of task (MET) hrs/wk. White blood cell (WBC) count, WBC ratios, and platelet count were derived. Multivariable regression analyses were used to estimate associations between leisure-time PA level and peripheral immune cell populations.

Results: A higher leisure-time PA level was associated with a lower WBC count (P_trend <0.001) and a lower neutrophil-to-lymphocyte ratio (NLR; P_trend=0.007). Leisure-time PA level was not associated with lymphocyte-to-monocyte ratio (LMR; P_trend=0.25) or platelet-to-lymphocyte ratio (PLR; P_trend=0.69). Participants with the highest leisure-time PA level had a lower odds of a high WBC count (>8.1×10⁹ cells/L; odds ratio [OR]: 0.76; 95% confidence interval [CI]: 0.66-0.88) and high NLR (>2.68; OR: 0.84; 95% CI: 0.72-0.99), which may predict CVD and all-cause mortality.

Conclusion: We observed an inverse association between leisure-time PA level, WBC count, and NLR, particularly for neutrophil levels. These results suggest that participants at higher levels of leisure-time PA may have lower levels of inflammation, which may be important for future chronic disease outcomes.

Background:Pregnancies complicated by gestational diabetes mellitus (GDM) pose substantial risks throughout the life course for mothers and offspring. Limited studies have evaluated the epigenome of mothers and offspring previously affected by GDM.

Objective(s):We sought to substantiate this area of research by evaluating top CpG hits from our epigenome-wide association analysis (EWAS) to ascertain potential differentially methylated regions (DMRs) associated with prior GDM exposure during pregnancy.

Methods:Our cohort comprised 137 mother-child dyads (GDM-OB=66 moms,61 kids; Non-GDM=71 moms,55 kids) with a GDM pregnancy 4-10 years prior. DNA was extracted from whole blood samples of mothers and kids using the Illumina EPIC array. Identification of DMRs was performed using the in R, setting a Bonferroni correction of P<0.05.

Results:None of the CpGs tested had regions with more than one CpG site. Offspring had 17 and 15 DMR candidates, adjusting for tanner stage, BMI, and body fat, respectively. After adjustment for body fat, mothers had 41 DMR candidates. The top hit in offspring for BMI and body fat had an inverse association with GDM, mapping to ANKRD9 (P=0.003; P=0.002, respectively). Data from the mothers had one positive association that mapped to TAPBP (P=0.039). These genes have been previously associated with BMI, height, and age at menopause.

Conclusion:Among the DMRs we identified, they hold the potential to explain the effects of GDM on mothers and their offspring and may help other studies target CpGs of interest. Subsequent studies should expand upon these associations to garner better insight into the epigenetic consequences of a GDM pregnancy.

Background: SARS-CoV-2 seroprevalence is commonly used to estimate population-level infection and vaccination history. However, seroprevalence cannot describe antibody titers and their ability to neutralize the virus, measures that are particularly important once most individuals have detectable antibodies from vaccination or infection.

Objective: To assess these traits, we studied quantitative binding antibody levels and neutralization activity among previously infected individuals in the United States over the course of the COVID-19 pandemic.

Methods: A convenience sample of residual clinical serum specimens with evidence of prior infection gathered during January 2021– February 2022 were selected from the CDC’s serial, cross-sectional, national commercial laboratory study of SARS-CoV-2 seroprevalence. Correlations between quantitative anti-receptor binding domain (anti-RBD) of the Spike protein antibody titers and neutralization capacity were calculated and anti-RBD antibody titers were examined by age group (<18, 18-49, 50-64, and >65 years) across four different SARS-CoV-2 variant epochs.

Results: Anti-RBD antibody titers were analyzed for 30,967 specimens with infection-induced antibodies of which 130 also had neutralizing assay results. In this subset, positive correlations between the two measures were observed in specimens from children and adults (correlation: 0.63; P <.01 for both). Mean anti-RBD antibody titers increased over the four variant epochs for all age groups (P <.01).

Conclusion: Anti-RBD antibody titers have generally increased over SARS-CoV-2 variant epochs and with increases in vaccination coverage. These increases, along with the correlation between anti-RBD titer and neutralization activity, likely indicate a progressive rise in immunity over the period studied in previously infected populations.