Common and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program.

All of Us is a biorepository aiming to advance biomedical research by providing various types of data in diverse human populations. Here we present a demonstration project validating the program's genomic data in 98,622 participants. We sought to replicate known genetic associations for three diseases (atrial fibrillation [AF], coronary artery disease, type 2 diabetes [T2D]) and two quantitative traits (height and low-density lipoprotein [LDL]) by conducting common and rare variant analyses. We identified one known risk locus for AF, five loci for T2D, 143 loci for height, and nine loci for LDL. In gene-based burden tests for rare loss-of-function variants, we replicated associations between TTN and AF, GIGYF1 and T2D, ADAMTS17, ACAN, NPR2 and height, APOB, LDLR, PCSK9 and LDL. Our results are consistent with previous literature, indicating that the All of Us program is a reliable resource for advancing the understanding of complex diseases in diverse human populations.

Association of Social Adversity with Comorbid Diabetes and Depression Symptoms in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study: A Syndemic Framework.

BACKGROUND: U.S. Hispanics/Latinos experience high lifetime risk for Type 2 diabetes and concurrent psychological depression. This comorbidity is associated with poorer self-management, worse disease outcomes, and higher mortality. Syndemic theory is a novel social epidemiological framework that emphasizes the role of economic and social adversity in promoting disease comorbidity and health disparities. PURPOSE: Informed by the syndemic framework, this study explored associations of socioeconomic and psychosocial adversity (low income/education, trauma history, adverse childhood experiences, ethnic discrimination, neighborhood problems [e.g., violence]) with comorbidity of diabetes and depression symptoms in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and Sociocultural Ancillary Study. METHODS: Participants were 5,247 Latino adults, aged 18-74, enrolled in four U.S. cities from 2008 to 2011. Participants completed a baseline physical exam and measures of depression symptoms and psychosocial adversity. Multinomial logistic regression analyses were conducted to examine associations of adversity variables with comorbid diabetes and high depression symptoms. RESULTS: Household income below $30,000/year was associated with higher odds of diabetes/depression comorbidity (odds ratio [OR] = 4.61; 95% confidence interval [CI]: 2.89, 7.33) compared to having neither condition, as was each standard deviation increase in adverse childhood experiences (OR = 1.41; 95% CI: 1.16, 1.71), ethnic discrimination (OR = 1.23; 95% CI: 1.01, 1.50), and neighborhood problems (OR = 1.53; 95% CI: 1.30, 1.80). CONCLUSION: Low household income, adverse childhood experiences, ethnic discrimination, and neighborhood problems are related to comorbid diabetes and depression in U.S. Latinos. Future studies should explore these relationships longitudinally.

Burden of Systolic and Diastolic Left Ventricular Dysfunction Among Hispanics in the United States: Insights From the Echocardiographic Study of Latinos.

BACKGROUND: Population-based estimates of cardiac dysfunction and clinical heart failure (HF) remain undefined among Hispanics/Latino adults. METHODS AND RESULTS: Participants of Hispanic/Latino origin across the United States aged 45 to 74 years were enrolled into the Echocardiographic Study of Latinos (ECHO-SOL) and underwent a comprehensive echocardiography examination to define left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction (LVDD). Clinical HF was defined according to self-report, and those with cardiac dysfunction but without clinical HF were characterized as having subclinical or unrecognized cardiac dysfunction. Of 1818 ECHO-SOL participants (mean age 56.4 years; 42.6% male), 49.7% had LVSD or LVDD or both. LVSD prevalence was 3.6%, whereas LVDD was detected in 50.3%. Participants with LVSD were more likely to be males and current smokers (all P<0.05). Female sex, hypertension, diabetes mellitus, higher body mass index, and renal dysfunction were more common among those with LVDD (all P<0.05). In age-sex adjusted models, individuals of Central American and Cuban backgrounds were almost 2-fold more likely to have LVDD compared with those of Mexican backgrounds. Prevalence of clinical HF with LVSD (HF with reduced EF) was 7.3%; prevalence of clinical HF with LVDD (HF with preserved EF) was 3.6%. 96.1% of the cardiac dysfunction seen was subclinical or unrecognized. Compared with those with clinical cardiac dysfunction, prevalent coronary heart disease was the only factor independently associated with subclinical or unrecognized cardiac dysfunction (odds ratio: 0.1; 95% confidence interval: 0.1-0.4). CONCLUSIONS: Among Hispanics/Latinos, most cardiac dysfunction is subclinical or unrecognized, with a high prevalence of diastolic dysfunction. This identifies a high-risk population for the development of clinical HF.

Socioeconomic status, nocturnal blood pressure dipping, and psychosocial factors: a cross-sectional investigation in Mexican-American women.

BACKGROUND: Despite established links between reduced nocturnal blood pressure (BP) dipping and cardiovascular disease, BP dipping research in Hispanics is limited. PURPOSE: This study investigated socioeconomic status (SES) as a predictor of BP dipping and the contributions of psychosocial factors to this relationship. Analyses were conducted for the overall sample and separately for higher and lower acculturated women. METHODS: Mexican-American women (N = 291; 40-65 years) reported demographics and completed psychosocial assessments and 36-h ambulatory BP monitoring. RESULTS: Lower SES related to reduced BP dipping in the overall sample and in more US-acculturated women (r's = .17-.30, p's < .05), but not in less-acculturated women (r's = .07, p's > .10). An indirect effect model from SES to BP dipping via psychosocial resources/risk fits well across samples. CONCLUSIONS: In Mexican-American women, the nature of SES gradients in BP dipping and the roles of psychosocial resources/risk differ by acculturation level.

Depression and cardiovascular sequelae in postmenopausal women. The Women's Health Initiative (WHI).

BACKGROUND: Subclinical depression, often clinically unrecognized, may pose increased risk of cardiovascular disease. Few studies have prospectively investigated cardiovascular events related to depression in older women. We describe prevalence, cardiovascular correlates, and relationship to subsequent cardiovascular events of depressive symptoms among generally healthy postmenopausal women. METHODS: The Women's Health Initiative Observational Study followed up 93 676 women for an average of 4.1 years. Depression was measured at baseline with a short form of the Center for Epidemiological Studies Depression Scale. Risks of cardiovascular disease (CVD) events were estimated from Cox proportional hazards models adjusting for multiple demographic, clinical, and risk factor covariates. RESULTS: Current depressive symptoms above the screening cutoff point were reported by 15.8% of women. Depression was significantly related to CVD risk and comorbidity (odds ratios ranging from 1.12 for hypertension to 1.60 for history of stroke or angina). Among women with no history of CVD, depression was an independent predictor of CVD death (relative risk, 1.50) and all-cause mortality (relative risk, 1.32) after adjustment for age, race, education, income, diabetes, hypertension, smoking, high cholesterol level requiring medication, body mass index, and physical activity. Taking antidepressant medications did not alter the depression-associated risks associated. CONCLUSIONS: A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD death and all-cause mortality, even after controlling for established CVD risk factors. Whether early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.