Social and scientific motivations to move beyond groups in allele frequencies: The TOPMed experience

For the genomics community, allele frequencies within defined groups (or “strata”) are useful across multiple research and clinical contexts. Benefits include allowing researchers to identify populations for replication or “look up” studies, enabling researchers to compare population-specific frequencies to validate findings, and facilitating assessment of variant pathogenicity in clinical contexts. However, there are potential concerns with stratified allele frequencies. These include potential re-identification (determining whether or not an individual participated in a given research study based on allele frequencies and individual-level genetic data), harm from associating stigmatizing variants with specific groups, potential reification of race as a biological rather than a socio-political category, and whether presenting stratified frequencies—and the downstream applications that this presentation enables—is consistent with participants’ informed consents. The NHLBI Trans-Omics for Precision Medicine (TOPMed) program considered the scientific and social implications of different approaches for adding stratified frequencies to the TOPMed BRAVO (Browse All Variants Online) variant server. We recommend a novel approach of presenting ancestry-specific allele frequencies using a statistical method based upon local genetic ancestry inference. Notably, this approach does not require grouping individuals by either predominant global ancestry or race/ethnicity and, therefore, mitigates re-identification and other concerns as the mixture distribution of ancestral allele frequencies varies across the genome. Here we describe our considerations and approach, which can assist other genomics research programs facing similar issues of how to define and present stratified frequencies in publicly available variant databases

Association of food parenting practice patterns with obesogenic dietary intake in Hispanic/Latino youth: Results from the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth)

Some food parenting practices (FPPs)are associated with obesogenic dietary intake in non-Hispanic youth, but studies in Hispanics/Latinos are limited. We examined how FPPs relate to obesogenic dietary intake using cross-sectional data from 1214 Hispanic/Latino 8-16-year-olds and their parents/caregivers in the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth). Diet was assessed with 2 24-h dietary recalls. Obesogenic items were snack foods, sweets, and high-sugar beverages. Three FPPs (Rules and Limits, Monitoring, and Pressure to Eat)derived from the Parenting strategies for Eating and Activity Scale (PEAS)were assessed. K-means cluster analysis identified 5 groups of parents with similar FPP scores. Survey-weighted multiple logistic regression examined associations of cluster membership with diet. Parents in the controlling (high scores for all FPPs)vs. indulgent (low scores for all FPPs)cluster had a 1.75 (95% CI: 1.02, 3.03)times higher odds of having children with high obesogenic dietary intake. Among parents of 12–16-year-olds, membership in the pressuring (high Pressure to Eat, low Rules and Limits and Monitoring scores)vs. indulgent cluster was associated with a 2.96 (95% CI: 1.51, 5.80)times greater odds of high obesogenic dietary intake. All other associations were null. Future longitudinal examinations of FPPs are needed to determine temporal associations with obesogenic dietary intake in Hispanic/Latino youth

Physical Activity and Sedentary Behavior among US Hispanic/Latino Youth: The SOL Youth Study

Purpose: Physical activity and sedentary behavior among diverse Hispanic/Latino youth in the United States is not well documented. The aim of this study was to describe physical activity and sedentary behavior among a representative sample of Hispanic/Latino youth from four US communities using accelerometry and self-reported measures. Methods: From 2012 to 2014, 1466 Hispanic/Latino youth ages 8 to 16 yr, children of participants in the Hispanic Community Health Study/Study of Latinos, enrolled in the SOL youth. Physical activity and sedentary behavior were assessed by interview. After this, youth wore an Actical accelerometer for 1 wk. All statistical analyses accounted for the complex survey design and used sampling weights. Results: The accelerometer wear time adjusted mean minutes per day was: 604.6, sedentary; 178.9, light; 25.4, moderate; and 10.2, vigorous. Generally, higher levels of moderate and vigorous activity occurred among males, Mexican backgrounds, and youth age 8 to 10 yr compared with older age groups. Higher levels of sedentary behavior occurred among youth age 15 to 16 yr compared with younger age groups. The most common activities (reported, ≥1 per month) were of lower intensity, including listening to music (91.9%), homework (87.0%), riding in car/bus (84.3%), and hanging out with friends (83.4%). Common active pursuits included travel by walking (74.6%), physical education class (71.7%), running (71.4%), and recess (71.3%). Conclusions: Time, intensity, and type of physical activity and sedentary behavior varied among Hispanic/Latino youth. These findings can inform efforts to increase physical activity and reduce sedentary behavior among US Hispanic/Latino youth

Objectively measured physical activity, sedentary behavior, and genetic predisposition to obesity in U.S. Hispanics/Latinos: Results from the hispanic community health study/study of Latinos (HCHS/SOL)

Studies using self-reported data suggest a gene-physical activity interaction on obesity, yet the influence of sedentary behavior, distinct from a lack of physical activity, on genetic associations with obesity remains unclear. We analyzed interactions of accelerometer-measured moderate to vigorous physical activity (MVPA) and time spent sedentary with genetic variants on obesity among 9,645 U.S. Hispanics/Latinos. An overall genetic risk score (GRS), a central nervous system (CNS)-related GRS, and a non-CNS-related GRS were calculated based on 97 BMIassociated single nucleotide polymorphisms (SNPs). Genetic association with BMI was stronger in individuals with lower MVPA (first tertile) versus higher MVPA (third tertile) (b = 0.78 kg/m2 [SE, 0.10 kg/m2] vs. 0.39 kg/m2 [0.09 kg/m2] per SD increment of GRS; Pinteraction = 0.005), and in those with more time spent sedentary (third tertile) versus less time spent sedentary (first tertile) (b = 0.73 kg/m2 [SE, 0.10 kg/m2] vs. 0.44 kg/m2 [0.09 kg/m2]; Pinteraction = 0.006). Similar significant interaction patterns were observed for obesity risk, body fat mass, fat percentage, fat mass index, and waist circumference, but not for fat-free mass. The CNS-related GRS, but not the non-CNS-related GRS, showed significant interactions with MVPA and sedentary behavior, with effects on BMI and other adiposity traits. Our data suggest that both increasing physical activity and reducing sedentary behavior may attenuate genetic associations with obesity, although the independence of these interaction effects needs to be investigated further

Structural social support and cardiovascular disease risk factors in Hispanic/Latino adults with diabetes: results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Objective(s): Cross-sectional and longitudinal studies have yielded inconsistent findings on the associations of social support networks with cardiovascular health in Hispanic/Latino adults with diabetes. We examined the cross-sectional associations of structural social support and traditional cardiovascular disease (CVD) risk factors in a diverse sample of Hispanic/Latino adults with diabetes. Research Design and Methods: This analysis included 2994 adult participants ages 18–74 with diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL–2008–2011). Select items from the Social Network Inventory (SNI) were used to assess indices of structural social support, i.e. network size (number of children, parents, and in-laws) and frequency of familial contact. Standardized methods were used to measure abdominal obesity, BMI, hypertension, hypercholesterolemia, and smoking status. Multivariate regression was used to examine associations of structural support with individual CVD risk factors with demographics, acculturation, physical health, and psychological ill-being (depressive symptoms and anxiety) included as covariates. Results: There were no significant cross-sectional associations of structural support indices with abdominal obesity, hypertension, hypercholesterolemia, or smoking status. There was a marginally significant (OR: 1.05; 95%CI 0.99–1.11) trend toward higher odds of obesity in participants reporting a larger family unit (including children, parents, and in-laws) and those with closer ties with extended family relatives (OR: 1.04; 95%CI 0.99–1.09). Conclusions: Structural social support was marginally associated with higher odds of obesity in Hispanic/Latino adults with diabetes. Alternate forms of social support (e.g. healthcare professionals, friends, peers) should be further explored as potential markers of cardiac risk in Hispanics/Latinos with diabetes

Associations between perceived neighborhood environment and cognitive function among middle-aged and older women and men: Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study

Purpose: To examine cross-sectional associations between perceived neighborhood environment and cognitive function among middle-aged and older Hispanic/Latino women and men. Methods: Data from the Hispanic Community Health Study/Study of Latinos (2008–2011) and its Sociocultural Ancillary Study (2009–2010) were used. Participants were Hispanic/Latino women (n = 1812) and men (n = 1034) aged 45–74 years. Survey-weighted linear regression models were used to examine associations between self-reported perceived neighborhood environment (i.e., neighborhood social cohesion and problems categorized as quintiles, and neighborhood safety from crime categorized as low, medium, or high) with cognitive function (i.e., global cognition, verbal learning, memory, verbal fluency, and processing speed scores) in women and men. Final model adjusted for age, Hispanic/Latino background, language, field site, household income, education, years lived in neighborhood, and depressive symptoms. Results: Women in the lowest quintile of perceived neighborhood problems (vs. highest quintile) had higher global cognition (β 0.48, 95% CI 0.03, 0.94, p trend 0.229) and memory scores (0.60, 95% CI 0.11, 1.09, p trend: 0.060). Women in the highest quintile of perceived neighborhood social cohesion (vs. lowest quintile) had lower global cognition (β − 0.56, 95% CI − 1.02, − 0.09, p trend 0.004), verbal learning (B − 1.01, 95% CI − 2.00, − 0.03, p trend 0.015), verbal fluency (B − 2.00, 95% CI − 3.83, − 0.16, p trend 0.006), and processing speed (B − 2.11, 95% CI − 3.87, − 0.36, p trend 0.009). There was no association between perceived neighborhood safety from crime and cognition among women, or between any perceived neighborhood environment measure and cognition among men. Conclusions: Middle-aged and older Hispanic/Latina women living in neighborhoods with the lowest perceived problems had higher global cognition and memory. Women living in neighborhoods with the highest perceived social cohesion had lower global cognition, verbal learning, verbal fluency, and processing speed

Extra-familial social factors and obesity in the Hispanic Community Children’s Health Study/Study of Latino Youth

Hispanic/Latino youth are disproportionately affected by obesity. However, how social factors outside of the family relate to Hispanic/Latino youth obesity is not well understood. We examined associations of extra-familial social factors with overweight/obesity prevalence, and their variation by sex and age, in 1444 Study of Latino Youth participants [48.6% female; 43.4% children (8–11 years); 56.6% adolescents (12–16 years)], who were offspring of the Hispanic Community Health Study/Study of Latinos participants. Youth self-reported general social support from friends, dietary-, and physical activity (PA)-specific support from peers, and awareness/internalization of thinness ideals. Overweight/obesity was defined as body mass index ≥ 85th percentile. Logistic regression models assessed effects of social factors and their interactions with age-group and sex, adjusting for potential confounders. Social support from friends interacted with both age and sex in relation to overweight/obesity. Female children who reported lesser (OR 0.60; 95% CI [0.39, 0.91]) and female adolescents who reported greater (OR 1.35; 95% CI [1.06, 1.74]) social support from friends had higher odds of overweight/obesity. Among males, greater awareness/internalization of thinness ideals related to higher odds of overweight/obesity (OR 2.30; 95% CI [1.59, 3.31]). Awareness/internalization of thinness ideals was not associated with overweight/obesity among females. Dietary and PA-specific peer support did not relate to overweight/obesity. Social support from friends and awareness/internalization of thinness ideals were significantly related to odds of overweight/obesity in Hispanic/Latino youth; associations varied by age and sex, and persisted after control for intra-familial factors (overall family support/function; diet and activity specific support)

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories

Associations of changes in fat free mass with risk for type 2 diabetes: Hispanic Community Health Study/Study of Latinos

To determine whether loss of muscle mass (approximated using fat free mass [FFM]) is associated with risk for type 2 diabetes mellitus (T2DM) in Hispanic/Latino adults in the United States. Participants were Hispanic/Latino adults (18–74-year-olds) who completed Visit 2 of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; multi-site, prospective cohort study; 6.1-year follow-up) and did not have T2DM at baseline (n = 6264). At baseline and Visit 2, FFM was measured using bioelectrical impedance analysis and fasting glucose, HbA1c, and fasting insulin were measured by examiners. Diabetes was defined according to American Diabetes Association criteria. Survey-weighted Poisson regression models examined the association of percent change in relative FFM (%ΔFFM) with incident prediabetes and T2DM. Survey-weighted multivariable regression models examined associations of %ΔFFM with changes in glucose and insulin measures. Relative FFM declined by 2.1% between visits. %ΔFFM was inversely associated with incident prediabetes (p-for-trend = 0.001) and with changes in glucose and insulin measures (p-for-trend <0.0001). Findings were null, except for HOMA-IR, after adjustment for changes in adiposity measures. Associations were generally stronger for individuals with baseline overweight/obesity. Reducing loss of FFM during adulthood may reduce prediabetes risk (primarily insulin resistance), particularly among individuals with overweight/obesity