Genetics of Obesity in Diverse Populations

Purpose of Review: The prevalence of obesity continues to rise, fueling a global public health crisis characterized by dramatic increases in type 2 diabetes, cardiovascular disease, and many cancers. In the USA, several minority populations, who bear much of the obesity burden (47% in African Americans and Hispanic/Latinos, compared to 38% in European descent groups), are particularly at risk of downstream chronic disease. Compounding these disparities, most genome-wide association studies (GWAS)—including those of obesity—have largely been conducted in populations of European or East Asian ancestry. In fact, analysis of the GWAS Catalog found that while the proportion of participants of non-European or non-Asian descent had risen from 4% in 2009 to 19% in 2016, African-ancestry participants are still just 3% of GWAS, Hispanic/Latinos are < 0.5%, and other ancestries are < 0.3% or not represented at all. This review summarizes recent developments in obesity genomics in US minority populations, with the goal of reducing obesity health disparities and improving public health programs and access to precision medicine. Recent Findings: GWAS of populations with the highest burden of obesity are essential to narrow candidate variants for functional follow-up, to identify additional ancestry-specific variants that contribute to individual genetic susceptibility, and to advance both public health and precision medicine approaches to obesity. Summary: Given the global public health burden posed by obesity and downstream chronic conditions which disproportionately affect non-European populations, GWAS of obesity-related traits in diverse populations is essential to (1) locate causal variants in GWAS-identified regions through fine mapping, (2) identify variants which influence obesity across ancestries through generalization, and (3) discover novel ancestry-specific variants which may be low frequency in European populations but common in other groups. Recent efforts to expand obesity genomic studies to understudied and underserved populations, including AAAGC, PAGE, and HISLA, are working to reduce obesity health disparities, improve public health, and bring the promise of precision medicine to all

Integration of Social, Cultural, and Biomedical Strategies into an Existing Couple-Based Behavioral HIV/STI Prevention Intervention: Voices of Latino Male Couples

Introduction Successful HIV prevention and treatment requires evidence-based approaches that combine biomedical strategies with behavioral interventions that are socially and culturally appropriate for the population or community being prioritized. Although there has been a push for a combination approach, how best to integrate different strategies into existing behavioral HIV prevention interventions remains unclear. The need to develop effective combination approaches is of particular importance for men who have sex with men (MSM), who face a disproportionately high risk of HIV acquisition. Materials and Methods We collaborated with Latino male couples and providers to adapt Connect ‘n Unite, an evidence-based intervention for Black male couples, for Latino male couples. We conducted a series of three focus groups, each with two cohorts of couples, and one focus group with providers. A purposive stratified sample of 20 couples (N = 40, divided into two cohorts) and 10 providers provided insights into how to adapt and integrate social, cultural, and biomedical approaches in a couples-based HIV/AIDS behavioral intervention. Results The majority (N = 37) of the couple participants had no prior knowledge of the following new biomedical strategies: non-occupational post-exposure prophylaxis (nPEP); pre-exposure prophylaxis (PrEP); and HIV self-testing kits. After they were introduced to these biomedical interventions, all participants expressed a need for information and empowerment through knowledge and awareness of these interventions. In particular, participants suggested that we provide PrEP and HIV self-testing kits by the middle or end of the intervention. Providers suggested a need to address behavioral, social and structural issues, such as language barriers; and the promotion of client-centered approaches to increase access to, adaptation of, and adherence to biomedical strategies. Corroborating what couple participants suggested, providers agreed that biomedical strategies should be offered after providing information about these tools. Regarding culturally sensitive and responsive approaches, participants identified stigma and discrimination associated with HIV and sexual identity as barriers to care, language barriers and documentation status as further barriers to care, the couple-based approach as ideal to health promotion, and the need to include family topics in the intervention. Discussion We successfully adapted an evidence-based behavioral HIV prevention intervention for Latino male couples. The adapted intervention, called Conectando Latinos en Pareja, integrates social, cultural, behavioral and biomedical strategies to address the HIV epidemic among Latino MSM. The study highlights the promise regarding the feasibility of implementing a combination approach to HIV prevention in this populatio

Syndemic factors associated with adult sexual HIV risk behaviors in a sample of Latino men who have sex with men in New York City

Objective: Syndemic theory has been proposed as a framework for understanding the role of multiple riskfactors driving the HIV epidemic among sexual and gender minority individuals. As yet, the frameworkhas been relatively absent in research on Latinos/as.Methods: We used logistic regression to assess relationships among cumulative syndemic conditions –including clinically significant depression, high-risk alcohol consumption, discrimination, and childhoodsexual abuse – engagement with multiple partners and condomless anal intercourse (CAI) in a sample of176 Latino men who have sex with men (MSM) in New York City.Results: In bivariate analyses, an increase in the number of syndemic factors experienced was associatedwith an increased likelihood of reporting multiple partners and CAI. In multivariable analyses, participantswith 2, 3, and 4 factors were significantly more likely to report multiple partners than those with 0(aOR = 4.66, 95% CI [1.29, 16.85); aOR = 7.28, 95% CI [1.94, 27.28] and aOR = 8.25, 95% CI [1.74, 39.24]respectively; p \u3c 0.05. Regarding CAI, only participants with 3 and 4 factors differed from those with 0aOR = 7.35, 95% CI [1.64, 32.83] and OR = 8.06, 95% CI [1.39, 46.73] respectively.Conclusions: Comprehensive approaches that address syndemic factors, and capitalize on resiliency, areneeded to address the sexual health needs of Latino MSM

Syndemic factors associated with adult sexual HIV risk behaviors in a sample of Latino men who have sex with men in New York City

Objective: Syndemic theory has been proposed as a framework for understanding the role of multiple riskfactors driving the HIV epidemic among sexual and gender minority individuals. As yet, the frameworkhas been relatively absent in research on Latinos/as.Methods: We used logistic regression to assess relationships among cumulative syndemic conditions –including clinically significant depression, high-risk alcohol consumption, discrimination, and childhoodsexual abuse – engagement with multiple partners and condomless anal intercourse (CAI) in a sample of176 Latino men who have sex with men (MSM) in New York City.Results: In bivariate analyses, an increase in the number of syndemic factors experienced was associatedwith an increased likelihood of reporting multiple partners and CAI. In multivariable analyses, participantswith 2, 3, and 4 factors were significantly more likely to report multiple partners than those with 0(aOR = 4.66, 95% CI [1.29, 16.85); aOR = 7.28, 95% CI [1.94, 27.28] and aOR = 8.25, 95% CI [1.74, 39.24]respectively; p \u3c 0.05. Regarding CAI, only participants with 3 and 4 factors differed from those with 0aOR = 7.35, 95% CI [1.64, 32.83] and OR = 8.06, 95% CI [1.39, 46.73] respectively.Conclusions: Comprehensive approaches that address syndemic factors, and capitalize on resiliency, areneeded to address the sexual health needs of Latino MSM

A pilot Internet "Value of Health" Panel: recruitment, participation and compliance

Objectives To pilot using a panel of members of the public to provide preference data via the Internet Methods A stratified random sample of members of the general public was recruited and familiarised with the standard gamble procedure using an Internet based tool. Health states were perdiodically presented in "sets" corresponding to different conditions, during the study. The following were described: Recruitment (proportion of people approached who were trained); Participation (a) the proportion of people trained who provided any preferences and (b) the proportion of panel members who contributed to each "set" of values; and Compliance (the proportion, per participant, of preference tasks which were completed). The influence of covariates on these outcomes was investigated using univariate and multivariate analyses. Results A panel of 112 people was recruited. 23% of those approached (n = 5,320) responded to the invitation, and 24% of respondents (n = 1,215) were willing to participate (net = 5.5%). However, eventual recruitment rates, following training, were low (2.1% of those approached). Recruitment from areas of high socioeconomic deprivation and among ethnic minority communities was low. Eighteen sets of health state descriptions were considered over 14 months. 74% of panel members carried out at least one valuation task. People from areas of higher socioeconomic deprivation and unmarried people were less likely to participate. An average of 41% of panel members expressed preferences on each set of descriptions. Compliance ranged from 3% to 100%. Conclusion It is feasible to establish a panel of members of the general public to express preferences on a wide range of health state descriptions using the Internet, although differential recruitment and attrition are important challenges. Particular attention to recruitment and retention in areas of high socioeconomic deprivation and among ethnic minority communities is necessary. Nevertheless, the panel approach to preference measurement using the Internet offers the potential to provide specific utility data in a responsive manner for use in economic evaluations and to address some of the outstanding methodological uncertainties in this field

Quantum Tunneling in Nuclear Fusion

Recent theoretical advances in the study of heavy ion fusion reactions below the Coulomb barrier are reviewed. Particular emphasis is given to new ways of analyzing data, such as studying barrier distributions; new approaches to channel coupling, such as the path integral and Green function formalisms; and alternative methods to describe nuclear structure effects, such as those using the Interacting Boson Model. The roles of nucleon transfer, asymmetry effects, higher-order couplings, and shape-phase transitions are elucidated. The current status of the fusion of unstable nuclei and very massive systems are briefly discussed.Comment: To appear in the January 1998 issue of Reviews of Modern Physics. 13 Figures (postscript file for Figure 6 is not available; a hard copy can be requested from the authors). Full text and figures are also available at http://nucth.physics.wisc.edu/preprints

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Findings from the Hispanic Community Health Study/Study of Latinos on the Importance of Sociocultural Environmental Interactors: Polygenic Risk Score-by-Immigration and Dietary Interactions

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 &lt; 0.0104), and healthy diet (p &lt; 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 &lt; 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 &lt; 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

Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

γδ T cells are considered to be innate-like lymphocytes that respond rapidly to stress without clonal selection and differentiation. Here we use next-generation sequencing to probe how this paradigm relates to human Vδ2neg T cells, implicated in responses to viral infection and cancer. The prevalent Vδ1 T cell receptor (TCR) repertoire is private and initially unfocused in cord blood, typically becoming strongly focused on a few high-frequency clonotypes by adulthood. Clonal expansions have differentiated from a naive to effector phenotype associated with CD27 downregulation, retaining proliferative capacity and TCR sensitivity, displaying increased cytotoxic markers and altered homing capabilities, and remaining relatively stable over time. Contrastingly, Vδ2+ T cells express semi-invariant TCRs, which are present at birth and shared between individuals. Human Vδ1+ T cells have therefore evolved a distinct biology from the Vδ2+ subset, involving a central, personalized role for the γδ TCR in directing a highly adaptive yet unconventional form of immune surveillance