Abstract
Introduction: Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We examined the role of gene–environment interactions to better characterize the sociocultural environmental determinants and their genome-scale interactions, which may contribute to missing heritability of obesity. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: PRSs were derived using genome-wide association study (GWAS) weights from a publicly available, large meta-analysis of European ancestry samples. Generalized linear models were run using a set of a priori acculturation-related and environmental factors measured at visit 1 (2008–2011) and visit 2 (2014–2016) in an analytic subsample of 8,109 unrelated individuals with genotypic, phenotypic, and complete case data at both visits. We evaluated continuous measures of BMI and waist-to-hip ratio. All models were weighted for complex sampling design, combined, and sex-stratified. Results: Overall, we observed a consistent increase of BMI with greater PRS across both visits. We found the best-fitting model adjusted for top five principal components of ancestry, sex, age, study site, Hispanic/Latino background genetic ancestry group, sociocultural factors and PRS interactions with age at immigration, years since first arrival to the United States (p < 0.0104), and healthy diet (p < 0.0036) and explained 16% of the variation in BMI. For every 1-SD increase in PRS, there was a corresponding 1.10 kg/m2 increase in BMI (p < 0.001). When these results were stratified by sex, we observed that this 1-SD effect of PRS on BMI was greater for women than men (1.45 vs. 0.79 kg/m2, p < 0.001). Discussion: We observe that age at immigration and the adoption of certain dietary patterns may play a significant role in modifying the effect of genetic risk on obesity. Careful consideration of sociocultural and immigration-related factors should be evaluated. The role of nongenetic factors, including the social environment, should not be overlooked when describing the performance of PRS or for promoting population health in understudied populations in genomics.
Highlights
Hispanic/Latinos experience a disproportionate burden of obesity
The weighted sample was 48.9% female, 41.7% considered to be obese, with 65.3% with an annual income of
PRSBMI approximated a normal distribution in the population as shown in Figure 1A, while Supplementary Figure S3 shows that our body mass index (BMI) distribution was right skewed, which is consistent with previous population-based studies of countries like the
Summary
Hispanic/Latinos experience a disproportionate burden of obesity. Acculturation to US obesogenic diet and practices may lead to an exacerbation of innate genetic susceptibility. We utilized polygenic risk scores (PRSs) for body mass index (BMI) to perform analyses of PRS-by-acculturation and other environmental interactors among self-identified Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). By 2030, the economic consequences of obesity if left unaddressed could represent up to $66 billion per year in the United States (Wang et al, 2011) and a concomitant increase in health sequelae, most notably cardiovascular disease (CVD), diabetes, cancer, and loss of quality-adjusted life years (National Heart, Lung, and Blood Institute 2013). Hispanic/Latino adults bear a disproportionate burden of obesity, as they are 1.2 times more likely to be obese than non-Hispanic Whites (OMH, 2020). The age-adjusted prevalence of obesity is approximately 42.6% obesity Hispanic adults in the United States (as compared with 37.7% among non-Hispanic White adults) (Flegal et al, 2012). There are observed gender disparities, wherein women have a higher prevalence of obesity than men, related, in part, to a complex set of sociocultural and other environmental factors or biologic sex-related differences (Kanter and Caballero 2012; Link and Reue 2017)
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