Featured Research
Effect of exercise and/or reduced calorie dietary interventions on breast cancer-related endogenous sex hormones in healthy postmenopausal women
Physical inactivity and being overweight are modifiable lifestyle risk factors that consistently have been associated with a higher risk of postmenopausal breast cancer in observational studies. One biologic hypothesis underlying this relationship may be via endogenous sex hormone levels. It is unclear if changes in dietary intake, physical activity, or both, are most effective in changing these hormone levels.
Intentional Injury and the Risk of Subsequent Hospitalization for Attempted Suicide
Trauma patients are at increased risk of suicidal behavior. The association between assault injury and subsequent suicidal behavior relative to unintentional injury remains under-studied. This study hypothesized that trauma patients with assault injuries would demonstrate greater risk of subsequent suicide attempt hospitalization compared to patients with unintentional injury.
Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies
Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.
Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function
Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12.
Reconciling the evaluation of co-morbidities among HIV care patients in two large data systems: the Medical Monitoring Project and CFAR Network of Integrated Clinical Systems
The estimated burden of chronic disease among people living with HIV (PLWH) varies considerably by data source, due to differences in case definitions, analytic approaches, and underlying patient populations. We evaluated the burden of diabetes (DM) and chronic kidney disease (CKD) in two large data systems that are commonly queried to evaluate health issues affecting HIV care patients: the Medical Monitoring Project (MMP), a nationally representative sample, and the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a clinical cohort. In order to reconcile these two data sources, we addressed issues common to observational data, including selection bias, missing data, and development of case definitions. The overall adjusted estimated prevalence of DM and CKD in MMP was 12.7% and 7.6%, respectively, and the overall prevalence of DM and CKD in CNICS was 9.9% and 8.3%, respectively; prevalence estimates increased with age in both data sources.
Comparison of 2 Treatment Models: Precision Medicine and Preventive Medicine
Precision medicine tends to medicalize conditions and risk factors, often within a gene-centric framework, and intense efforts to identify and target subgroups may ignore or overlook the mismatch between the burden and causes of disease in the United States. What is needed are public health efforts to increase prevention of cancer and cardiovascular disease and to reduce social and racial disparities as well as inequalities in education, income, and opportunities. For medical treatments, one-size-fits-all treatments that are known to be effective will continue to work well until or unless convincing evidence becomes available that targeting subgroups actually improves health outcomes.
The mutational landscape of recurrent versus nonrecurrent human papillomavirus-related oropharyngeal cancer
Human papillomavirus-related (HPV-related) oropharyngeal squamous cell carcinomas (OPSCCs) have an excellent response rate to platinum-based chemoradiotherapy. Genomic differences between primary HPV-related OPSCCs that do or do not recur are unknown. Furthermore, it is unclear if HPV-related OPSCCs that recur share a genomic landscape with HPV-negative head and neck cancers (HNCs).
Depression during pregnancy and preterm delivery: a prospective cohort study among women attending antenatal clinic at Pumwani Maternity Hospital
Preterm birth occurs among 9.6% of births worldwide and is the leading cause of long-term neurodevelopmental disabilities among children and also responsible for 28% of neonatal deaths. No single etiological factor is responsible for preterm birth, but various risk factors have been identified. Prior studies have reported that compromised maternal mental health occurring during pregnancy may lead to various adverse obstetric outcomes.
The Effect of Depression on Adherence to Oral PrEP Among Men and Women in East Africa
Low adherence can undermine the efficacy of daily oral pre-exposure prophylaxis (PrEP). Mental health conditions, particularly depression, could be associated with low PrEP adherence, especially for women.
PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation.
