Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Considerations, Caveats, and Suggestions for the Use of Polygenic Scores for Social and Behavioral Traits.

Polygenic scores (PGS) are increasingly being used for prediction of social and behavioral traits, but suffer from many methodological, theoretical, and ethical concerns that profoundly limit their value. Primarily, these scores are derived from statistical correlations, carrying no inherent biological meaning, and thus may capture indirect effects. Further, the performance of these scores depends upon the diversity of the reference populations and the genomic panels from which they were derived, which consistently underrepresent minoritized populations, leading to poor fit when applied to diverse groups. There is also inherent danger of eugenic applications for the information gained from these scores, and general risk of misunderstandings that could lead to stigmatization for underrepresented groups. We urge extreme caution in use of PGS particularly for social/behavioral outcomes fraught for misinterpretation, with potential harm for the minoritized groups least likely to benefit from their use.

Genomic supremacy: the harm of conflating genetic ancestry and race.

BACKGROUND: Recent studies have reignited the tinderbox of debate surrounding the use of race and ancestry in medicine. These controversial studies have argued for a strong correlation between genetic ancestry and race, justifying continued use of genetic ancestry measures in studies of disease. These studies contend that increased use of continental ancestry estimates can inform clinical risk assessments and management. Further, recent studies of racial corrections used in clinical algorithms, such as those used to estimate 'normal' lung function, also advocate for use of genetic ancestry in place of race for refining risk algorithms. MAIN BODY: These positions are misleading, harmful, and reflect superficial interpretations of population genetics. In this Perspective, we argue that continental genetic ancestry, often proxied by race, serves as a poor indicator of disease risk, and reinforces racialized inequities. CONCLUSION: Instead, we endorse that racial disparities in disease should be investigated by rigorous measures of structural racism alongside careful measures of genetic factors in relevant disease pathways, rather than relying on genetic ancestry or race as a crude proxy for disease-causing alleles.

Changes in mental health symptoms and sociocultural factors across the COVID-19 pandemic in mothers of Mexican descent.

Latinos have been disproportionately affected by the COVID-19 pandemic in the US. Little is known about the lasting effects on mental health, particularly among mothers of young children, who historically report high levels of depression and anxiety. We examined if anxiety and depression symptoms worsened for mothers of Mexican descent across the pandemic and identified the role of sociocultural risk and protective factors on these changes. Mothers of Mexican descent (n = 141) with young children (ages 0-7) were administered surveys on mental health symptoms (anxiety and depression), stress-related sociocultural factors (perceived discrimination) before (pre-pandemic), within 3 months (early pandemic), and 18 months after the COVID-19 stay-at-home order (late pandemic). Another sociocultural factor, acculturative stress, was only measured pre-pandemic while during the later phase of the pandemic mothers reported their levels of loneliness, optimism, and coping styles. Repeated measures (RM) ANOVA demonstrated that depressive and anxiety symptoms as well as perceived discrimination increased from pre to early months of the COVID-19 pandemic and slightly lowered in late-COVID but did not return to pre-COVID levels. Two-way RM ANOVA showed that acculturative stress and perceived discrimination predicted worse mental health trajectories across the pandemic while moderations revealed that optimism buffered against, and avoidant coping increased the adverse effects of sociocultural factors on mental health. The effects of the COVID pandemic on mental health are lingering in mothers of young children; however, optimism may be a protective factor. The results also highlight the damaging effects of external factors, such as discrimination, on maternal mental health during times of crisis.

Optimism and Social Support Predict Healthier Adult Behaviors Despite Socially Disadvantaged Childhoods.

BACKGROUND: Studies have shown adverse effects of a disadvantaged childhood on adult health-promoting behaviors and related outcomes. Optimism and social support have been linked to greater likelihood of engaging in healthy behavior, but it is unclear whether these positive psychosocial factors may buffer harmful effects of early adversity. This study aims to determine if optimism and social support in adulthood can modify effects of childhood disadvantage on health behavior-related outcomes. METHODS: Longitudinal data were analyzed from a subset of participants in a US birth cohort established in 1959-1966 (ns of 681-840, per outcome). An index of childhood social disadvantage was derived from adverse socioeconomic and family stability factors reported by mothers at child's birth and age 7 years. Health behavior-related outcomes were self-reported when participants were of mean age 47 years. Multivariable adjusted robust Poisson regressions were performed. RESULTS: Regardless of level of childhood social disadvantage, we found higher levels of optimism and social support were both associated with higher probabilities of being a non-smoker (relative risk [RR]optimism = 1.17, 95% confidence interval [CI] = 1.09-1.26; RRsocial support = 1.24, 95%CI = 1.11-1.39), having a healthy diet (RRoptimism = 1.25, 95%CI = 1.10-1.43; RRsocial support = 1.27, 95%CI = 1.04-1.56), and a healthy body mass index (RRoptimism = 1.18, 95%CI = 1.00-1.40; RRsocial support = 1.29, 95%CI = 1.00-1.66). Interactions link higher optimism or social support with lower risk of smoking among those with moderate childhood disadvantage. CONCLUSIONS: Overall, these findings are consistent with the possibility that positive psychosocial resources contribute to maintaining a healthy lifestyle in mid-adulthood and may buffer effects of childhood social disadvantage.

Stress across generations: A qualitative study of stress, coping, and caregiving among Mexican immigrant mothers.

OBJECTIVE: Hispanic immigrants represent the largest and fastest growing ethnic minority within the US, justifying increased attention to identify factors that influence declining immigrant health across generations. This study investigates the range of psychosocial stress exposures and coping mechanisms of Mexican immigrant mothers, and implications for the health of their US-born children. DESIGN: We conducted 10 focus groups with 1st generation Mexican-born immigrant mothers (n = 32 women) in Nashville, TN, in the summer of 2014. Focus groups elicited challenges and benefits of life as an immigrant mother. Data were analyzed using a modified grounded theory approach. RESULTS: We identified four themes that indicate how maternal stressors could impact children's health: (1) work-family tradeoff, (2) limited freedom/mobility, (3) reduction of social networks, and (4) transmission of anxiety and fears to children. Women in our study also engage in a range of coping mechanisms, including the creation of new social networks, seeking support in religion, and seeking help from community resources. CONCLUSION: These results highlight the importance of developing new questionnaires to elicit stress exposures for Mexican immigrant mothers. Findings also suggest the value of intervention strategies and social policies that would ultimately improve maternal and child health in this marginalized population.

Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity.

BACKGROUND: The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity. RESULTS: Genome-wide DNA methylation was conducted on 92 saliva samples collected from Hispanic preschool children using the Infinium Illumina HumanMethylation 450 K BeadChip (Illumina, San Diego, CA, USA), which interrogates >484,000 CpG sites associated with ~24,000 genes. The analysis was limited to 936 genes that have been associated with obesity in a prior GWAS Study. Child DNA methylation at 17 CpG sites was found to be significantly associated with maternal BMI, with increased methylation at 12 CpG sites and decreased methylation at 5 CpG sites. Pathway analysis revealed methylation at these sites related to homocysteine and methionine degradation as well as cysteine biosynthesis and circadian rhythm. Furthermore, eight of the 17 CpG sites reside in genes (FSTL1, SORCS2, NRF1, DLC1, PPARGC1B, CHN2, NXPH1) that have prior known associations with obesity, diabetes, and the insulin pathway. CONCLUSIONS: Our study confirms that saliva is a practical human tissue to obtain in community settings and in pediatric populations. These salivary findings indicate potential epigenetic differences in Hispanic preschool children at risk for pediatric obesity. Identifying early biomarkers and understanding pathways that are epigenetically regulated during this critical stage of child development may present an opportunity for prevention or early intervention for addressing childhood obesity. TRIAL REGISTRATION: The clinical trial protocol is available at ClinicalTrials.gov ( NCT01316653 ). Registered 3 March 2011.

DNA methylation at stress-related genes is associated with exposure to early life institutionalization.

OBJECTIVES: Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the proportion of time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. MATERIALS AND METHODS: We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. RESULTS: An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. DISCUSSION: These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. Am J Phys Anthropol 161:84-93, 2016.. © 2016 Wiley Periodicals, Inc.

Early childhood social disadvantage is associated with poor health behaviours in adulthood.

BACKGROUND: Individual health behaviours are considered important risk factors for cardiometabolic diseases. These behaviours may be socially patterned by early exposure to social disadvantage, but few studies have prospectively tested this hypothesis empirically. AIM: This study investigated whether childhood social disadvantage was associated with likelihood of engaging in less healthy behaviours 40 years later. SUBJECTS AND METHODS: Prospective data were analysed from the New England Family Study, a 2005-2007 adult follow-up of a cohort initiated in 1959-1966 (n = 565). Childhood social environment (age 7 years) was assessed using a cumulative index of socioeconomic and family stability factors. Logistic regression models evaluated associations between social disadvantage and each health-related behaviour and obesity in adulthood. RESULTS: Relative to low disadvantage, higher disadvantage was associated with 3.6-fold greater odds of smoking (95% CI = 1.9-7.0), 4.8-fold greater odds (in women only) of excess alcohol consumption (95% CI = 1.6-14.2) and 2.7-fold greater odds of obesity (95% CI = 1.3-5.5), but was not associated with unhealthy diet or physical inactivity. CONCLUSION: These findings suggest childhood social disadvantage may contribute to adult cardiometabolic disease by predisposing children to adopt certain unhealthy behaviours. If replicated, such findings may support intervention strategies that target social environmental factors and behavioural pathways that are established early in life.

Epigenetics for anthropologists: An introduction to methods.

The study of epigenetics, or chemical modifications to the genome that may alter gene expression, is a growing area of interest for social scientists. Anthropologists and human biologists are interested in epigenetics specifically, as it provides a potential link between the environment and the genome, as well as a new layer of complexity for the study of human biological variation. In pace with the rapid increase in interest in epigenetic research, the range of methods has greatly expanded over the past decade. The primary objective of this article is to provide an overview of the current methods for assaying DNA methylation, the most commonly studied epigenetic modification. We will address considerations for all steps required to plan and conduct an analysis of DNA methylation, from appropriate sample collection, to the most commonly used methods for laboratory analyses of locus-specific and genome-wide approaches, and recommendations for statistical analyses. Key challenges in the study of DNA methylation are also discussed, including tissue specificity, the stability of measures, timing of sample collection, statistical considerations, batch effects, and challenges related to analysis and interpretation of data. Our hope is that this review serves as a primer for anthropologists and human biologists interested in incorporating epigenetic data into their research programs.

Childhood social disadvantage, cardiometabolic risk, and chronic disease in adulthood.

Adverse social environments in early life are hypothesized to become biologically embedded during the first few years of life, with potentially far-reaching implications for health across the life course. Using prospective data from a subset of a US birth cohort, the Collaborative Perinatal Project, started in 1959-1966 (n = 566), we examined associations of social disadvantage assessed in childhood with cardiometabolic function and chronic disease status more than 40 years later (in 2005-2007). Social disadvantage was measured with an index that combined information on adverse socioeconomic and family stability factors experienced between birth and age 7 years. Cardiometabolic risk (CMR) was assessed by combining information from 8 CMR biomarkers; an index of chronic disease status was derived by assessing 8 chronic diseases. Poisson models were used to investigate associations between social disadvantage and CMR or chronic disease scores while adjusting for childhood covariates and potential pathway variables. A high level of social disadvantage was significantly associated with both higher CMR (incident rate ratio = 1.69, 95% confidence interval: 1.19, 2.39) and with a higher number of chronic diseases (incident rate ratio = 1.39, 95% confidence interval: 1.00, 1.92) in minimally adjusted models. Associations with CMR persisted even after accounting for childhood and adult covariates.

Childhood adversity, adult neighborhood context, and cumulative biological risk for chronic diseases in adulthood.

OBJECTIVE: We examined the association between childhood adversity and cumulative biological risk for a variety of chronic diseases in adulthood, and whether this association varied by neighborhood affluence. METHODS: Data were drawn from the Chicago Community Adult Health Study (2001-2003), a cross-sectional probability sample that included interviews and blood collection (n = 550 adults). A childhood adversity score was calculated from eight items. Neighborhood affluence was defined using Census data. An index to reflect cumulative biological risk was constructed as a count of eight biomarkers above clinically established thresholds, including systolic and diastolic blood pressure, resting heart rate, C-reactive protein, waist circumference, hemoglobin A1c, and total and high-density lipoprotein cholesterol. Generalized linear models with a Poisson link function were used to estimate incident rate ratios (IRRs). RESULTS: A 1-standard-deviation increase in the childhood adversity score was associated with a 9% increase in cumulative biological risk, after adjustment for demographic and behavioral characteristics (IRR = 1.09, 95% confidence interval (CI) = 1.02-1.17). This association was modified by neighborhood affluence (IRR = 0.92, 95% CI = 0.86, 0.99). Stratified models indicated that childhood adversity was associated with elevated cumulative biological risk only among individuals who resided in low-affluence (bottom tertile) neighborhoods (IRR = 1.16, 95% CI = 1.05, 1.28); there was no association in high-affluence (top tertile) neighborhoods (IRR = 0.97, 95% CI = 0.83, 1.14). CONCLUSIONS: Childhood adversity is associated with elevated cumulative biological risk in adulthood, and neighborhood affluence may buffer this association. Results demonstrate the importance of neighborhood characteristics for associations between childhood adversity and disease risk, even after accounting for adult socioeconomic status.

Integrating genetic and socioeconomic data to predict the progression of nonalcoholic fatty liver disease.

OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics. MATERIALS AND METHODS: We cross-sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD. RESULTS: Adjusting for age, sex, body mass index, and PNPLA3 genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% confidence interval [CI]: 1.21-8.76, p = 0.019), an effect comparable to that of possessing the major PNPLA3 risk variant. Notably, the effect of PNPLA3 genotype on advanced fibrosis was attenuated to nonsignificance following adjustment for education and other socioeconomic markers. The effect of the protective HSD17B13 variant, moreover, diminished after adjustment for education (odds ratio [OR]: 0.39 [95% CI: 0.13-1.16, p = 0.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an OR of 8.0 (95% CI: 1.91-33.86, p = 0.005). DISCUSSION: Adjusting for education attenuated the effects of genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors-rather than genes or ethnicity-may be driving disease severity within some populations. Findings reveal the importance of including socioenvironmental controls when considering the role of genetics or ethnicity in complex disease.

Clinicians' perspectives on race-specific guidelines for hypertensive treatment.

Despite the general consensus that there is no biological basis to race, racial categorization is still used by clinicians to guide diagnosis and treatment plans for certain diseases. In medicine, race is commonly used as a rough proxy for unmeasured social, environmental, and genetic factors. The American College of Cardiology's Eighth Joint National Committee's (JNC 8) guidelines for the treatment of hypertension provide race-specific medication recommendations for Black versus non-Black patients, without strong evidence for race-specific physiological differences in drug response. Clinicians practicing family or geriatric medicine (n = 21) were shown a video of a mock hypertensive patient with genetic ancestry test results that could be viewed as discordant with their phenotype and self-identified race. After viewing the videos, we conducted in-depth interviews to examine how clinicians value and prioritize different cues about race -- namely genetic ancestry data, phenotypic appearance, and self-identified racial classifications - when making treatment decisions in the context of race-specific guidelines, particularly in situations when patients claim mixed-race or complex racial identities. Results indicate that clinicians inconsistently follow the race-specific guidelines for patients whose genetic ancestry test results do not match neatly with their self-identified race or phenotypic features. However, many clinicians also emphasized the importance of clinical experience, side effects, and other factors in their decision making. Clinicians' definitions of race, categorization of the patient's race, and prioritization of racial cues greatly varied. The existence of the race-specific guidelines clearly influences treatment decisions, even as clinicians' express uncertainty about how to incorporate consideration of a patient's genetic ancestry. In light of widespread debate about removal of race from medical diagnostics, researchers should revisit the clinical justification for maintaining these race-specific guidelines. Based on our findings and prior studies indicating a lack of convincing evidence for biological differences by race in medication response, we suggest removing race from the JNC 8 guidelines to avoid risk of perpetuating or exacerbating health disparities in hypertension.

Solutions From Mexican-Descent Perinatal Women To Pandemic-Related Food, Mental Health, And Health And Safety Stressors.

Latina women in the US were disproportionately affected by the COVID-19 pandemic because of structural racism, including discrimination, reduced care access, and elevated risk for illness and death. Although several US policies were implemented to offset the economic toll of the pandemic, few addressed complex stressors, particularly those among Mexican-descent mothers. This qualitative study with thirty-eight perinatal women and mothers of young children who were of Mexican descent sought to identify pandemic-related stressors and solicit recommendations for addressing them during future large-scale crises. Identified stressors included food access issues, mental health needs, and health and safety concerns. The women's recommendations revealed feasible and actionable strategies, including increased access to behavioral and health care services and accessible information about food-related resources. The findings highlight the critical need for responsive policies and programs to ensure the well-being of Mexican-descent perinatal women and mothers of young children during large-scale crises.

Is it time to end race and ethnicity adjustment for pediatric pulmonary function tests?

The continued inclusion of race in spirometry reference equations is a topic of intense debate for adult lung function, but less discussion has focused on implications for children. Obtaining accurate estimates of children's lung function is an important component of the diagnosis of childhood respiratory illnesses, including asthma, cystic fibrosis, and interstitial lung disease. Given the higher burden among racial/ethnic minorities for many respiratory illnesses, it is critical to avoid racial bias in interpreting lung function. We recommend against the continued use of race-specific reference equations for a number of reasons. The original reference populations used to develop the equations were comprised of children with restricted racial diversity, relatively small sample sizes, and likely included some unhealthy children. Moreover, there is no scientific justification for innate racial differences in lung function, as there is no clear physiological or genetic explanation for the disparities. Alternatively, many environmental factors harm lung development, including allergens from pests, asbestos, lead, prenatal smoking, and air pollution, as well as preterm birth and childhood respiratory illnesses, which are all more common among minority racial groups. Race-neutral equations may provide a temporary solution, but still rely on the racial diversity of the reference populations used to build them. Ultimately researchers must uncover the underlying factors truly driving racial differences in lung function.