Air pollution and epigenetic aging among Black and White women in the US.

BACKGROUND: DNA methylation-based measures of biological aging have been associated with air pollution and may link pollutant exposures to aging-related health outcomes. However, evidence is inconsistent and there is little information for Black women. OBJECTIVE: We examined associations of ambient particulate matter <2.5 µm and <10 µm in diameter (PM2.5 and PM10) and nitrogen dioxide (NO2) with DNA methylation, including epigenetic aging and individual CpG sites, and evaluated whether associations differ between Black and non-Hispanic White (NHW) women. METHODS: Validated models were used to estimate annual average outdoor residential exposure to PM2.5, PM10, and NO2 in a sample of self-identified Black (n=633) and NHW (n=3493) women residing in the contiguous US. We used sampling-weighted generalized linear regression to examine the effects of pollutants on six epigenetic aging measures (primary: DunedinPACE, GrimAgeAccel, and PhenoAgeAccel; secondary: Horvath intrinsic epigenetic age acceleration [EAA], Hannum extrinsic EAA, and skin & blood EAA) and epigenome-wide associations for individual CpG sites. Wald tests of nested models with and without interaction terms were used to examine effect measure modification by race/ethnicity. RESULTS: Black participants had higher median air pollution exposure than NHW participants. GrimAgeAccel was associated with both PM10 and NO2 among Black participants, (Q4 versus Q1, PM10: ß=1.09, 95% CI: 0.16-2.03; NO2: ß=1.01, 95% CI 0.08-1.94) but not NHW participants (p-for-heterogeneity: PM10=0.10, NO2=0.20). In Black participants, we also observed a monotonic exposure-response relationship between NO2 and DunedinPACE (Q4 versus Q1, NO2: ß=0.029, 95% CI: 0.004-0.055; p-for-trend=0.03), which was not observed in NHW participants (p-for-heterogeneity=0.09). In the EWAS, pollutants were significantly associated with differential methylation at 19 CpG sites in Black women and one in NHW women. CONCLUSIONS: In a US-wide cohort study, our findings suggest that air pollution is associated with DNA methylation alterations consistent with higher epigenetic aging among Black, but not NHW, women.

Branched chain amino acids harbor distinct and often opposing effects on health and disease.

BACKGROUND: The branched chain amino acids (BCAA) leucine, isoleucine, and valine are essential nutrients that have been associated with diabetes, cancers, and cardiovascular diseases. Observational studies suggest that BCAAs exert homogeneous phenotypic effects, but these findings are inconsistent with results from experimental human and animal studies. METHODS: Hypothesizing that inconsistencies between observational and experimental BCAA studies reflect bias from shared lifestyle and genetic factors in observational studies, we used data from the UK Biobank and applied multivariable Mendelian randomization causal inference methods designed to address these biases. RESULTS: In n = 97,469 participants of European ancestry (mean age = 56.7 years; 54.1% female), we estimate distinct and often opposing total causal effects for each BCAA. For example, of the 117 phenotypes with evidence of a statistically significant total causal effect for at least one BCAA, almost half (44%, n = 52) are associated with only one BCAA. These 52 associations include total causal effects of valine on diabetic eye disease [odds ratio = 1.51, 95% confidence interval (CI) = 1.31, 1.76], valine on albuminuria (odds ratio = 1.14, 95% CI = 1.08, 1.20), and isoleucine on angina (odds ratio = 1.17, 95% CI = 1.31, 1.76). CONCLUSIONS: Our results suggest that the observational literature provides a flawed picture of BCAA phenotypic effects that is inconsistent with experimental studies and could mislead efforts developing novel therapeutics. More broadly, these findings motivate the development and application of causal inference approaches that enable 'omics studies conducted in observational settings to account for the biasing effects of shared genetic and lifestyle factors.

The three branched chain amino acids (BCAAs) leucine, isoleucine, and valine are important building blocks of muscle proteins that are obtained from the diet. Many studies in human populations have examined whether BCAAs affect health and disease. These human studies report results that are inconsistent with results from highly controlled animal studies. Because interest in the therapeutic targeting of BCAAs is growing, we wanted to better understand these discrepancies. Briefly, we used data from a large database that captured many diseases (e.g., cardiovascular disease, cancers, and respiratory disease) and new statistical methods. Our results showed that discrepancies between human studies and animal studies may reflect errors in the ways human studies were designed and conducted. As a result, these human studies may provide a flawed picture of BCAA effects that could mislead efforts developing novel therapeutics.

The Economic Burden of Adults with Major Depressive Disorder in the United States (2010 and 2018).

BACKGROUND: The incremental economic burden of US adults with major depressive disorder (MDD) was estimated at $US210.5 billion in 2010 (year 2012 values). OBJECTIVE: Following a similar methodology, this study updates the previous findings with more recent data to report the economic burden of adults with MDD in 2018. METHOD: This study used a framework for evaluating the incremental economic burden of adults with MDD in the USA that combined original and literature-based estimates, focusing on key changes between 2010 and 2018. The prevalence rates of MDD by sex, age, employment, and treatment status over time were estimated based on the National Survey on Drug Use and Health (NSDUH). The incremental direct and workplace costs per individual with MDD were primarily derived from administrative claims data and NSDUH data using comparative analyses of individuals with and without MDD. Societal direct and workplace costs were extrapolated by multiplying NSDUH estimates of the number of people with MDD by the direct and workplace cost estimates per patient. The suicide-related costs were estimated using a human capital method. RESULTS: The number of US adults with MDD increased by 12.9%, from 15.5 to 17.5 million, between 2010 and 2018, whereas the proportion of adults with MDD aged 18-34 years increased from 34.6 to 47.5%. Over this period, the incremental economic burden of adults with MDD increased by 37.9% from $US236.6 billion to 326.2 billion (year 2020 values). All components of the incremental economic burden increased (i.e., direct costs, suicide-related costs, and workplace costs), with the largest growth observed in workplace costs, at 73.2%. Consequently, the composition of 2018 costs changed meaningfully, with 35% attributable to direct costs (47% in 2010), 4% to suicide-related costs (5% in 2010), and 61% to workplace costs (48% in 2010). This increase in the workplace cost share was consistent with more favorable employment conditions for those with MDD. Finally, the proportion of total costs attributable to MDD itself as opposed to comorbid conditions remained stable at 37% (38% in 2010). CONCLUSION: Workplace costs accounted for the largest portion of the growing economic burden of MDD as this population trended younger and was increasingly likely to be employed. Although the total number of adults with MDD increased from 2010 to 2018, the incremental direct cost per individual declined. At the same time, the proportion of adults with MDD who received treatment remained stable over the past decade, suggesting that substantial unmet treatment needs remain in this population. Further research is warranted into the availability, composition, and quality of MDD treatment services.