Background Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease (CVD), range from 34 to 50%. Genetic variants so far identified by genome-wide association (GWA) studies only explain a small proportion (< 2%) of its variation. Methods and Results We conducted a meta-analysis of 28 GWA studies, including more than 90,000 subjects of European ancestry, the first GWA meta-analysis of fibrinogen levels in 7 African Americans studies totaling 8,289 samples, and a GWA study in Hispanic-Americans totaling 1,366 samples. Evaluation for association of SNPs with clinical outcomes included a total of 40,695 cases and 85,582 controls for coronary artery disease (CAD), 4,752 cases and 24,030 controls for stroke, and 3,208 cases and 46,167 controls for venous thromboembolism (VTE). Overall, we identified 24 genome-wide significant (P<5×10−8) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the three structural fibrinogen genes and pathways related to inflammation, adipocytokines and thyrotrophin-releasing hormone signaling. Whereas lead SNPs in a few loci were significantly associated with CAD, the combined effect of all 24 fibrinogen-associated lead SNPs was not significant for CAD, stroke or VTE. Conclusion We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and CAD, stroke or VTE.

Objective The objective of this paper is to describe baseline differences between obese and non-obese endometrial cancer survivor in anthropometrics, exercise behavior, fitness, heart rate and blood pressure, and quality of life, and to analyze whether the effect of a home-based exercise intervention on these outcomes differed for obese and non-obese participants. Methods One hundred post-treatment Stage I–IIIa endometrial cancer survivors participated in a single arm 6 month study in which they received a home-based exercise intervention. Cardiorespiratory fitness, anthropometrics, and exercise behavior were measured every two months, and quality of life (QOL) and psychological distress were measured at baseline and 6 months. Results Adjusting for potential confounders, at baseline obese survivors had poorer cardiorespiratory fitness (p=.002), higher systolic blood pressure (p=.018), and lower physical functioning (p<.001) and ratings of general health (p=.002), and more pain (p=.037) and somatization (.002). Significant improvements were seen in exercise behavior, resting heart rate, systolic blood pressure, and multiple QOL domains over the course of the intervention. Obese survivors had less improvement in exercise behavior and cardiorespiratory fitness than non-obese survivors, but there were no differences with regard to improvements in QOL and stress. Conclusions Home based exercise interventions are beneficial to endometrial cancer survivors, including those whose BMI is in the obese range. While obese survivors have lower levels of physical activity and fitness, they experienced similar activity, fitness, quality of life and mental health benefits. Exercise should be encouraged in endometrial cancer survivors, including those who are obese.

Objective This study evaluated the effect of two home-based exercise interventions (one culturally-adapted and one standard) on changes in Social Cognitive Theory (SCT) variables, physical activity (PA) and sedentary time (ST), and to determine the association between changes in SCT variables and changes in PA and ST in Hispanic breast cancer survivors. Method Project VIVA! was a 16-week randomized controlled pilot study to test the effectiveness and feasibility of a culturally-adapted exercise intervention for Mexican American and Puerto Rican breast cancer survivors in Houston, Texas and San Juan, Puerto Rico, respectively. Women (N=89) completed questionnaires on SCT variables, PA and ST and were then randomized to a 16-week culturally-adapted exercise program, a non-culturally adapted standard exercise intervention or a wait-list control group. Multiple regression models were used to determine associations between changes in SCT variables and changes in PA and ST. Results Participants were in their late 50s (58.5 ± 9.2 years) and obese (31.0 ± 6.5 kg/m2). Women reported doing roughly 34.5 minutes/day of PA and spending over 11 hours/day in sedentary activities. Across groups, women reported significant increases in exercise self-efficacy and moderate-intensity, vigorous-intensity, and total physical activity from baseline to follow-up (p<.05). Increased social support from family was associated with increases in vigorous-intensity PA. Increases in social modeling were associated with increases in moderate-intensity and total PA and decreases in ST from baseline to follow-up (p<.05). Conclusions Hispanic cancer survivors benefit from PA interventions that focus on increasing social support from family and friends and social modeling.

Objective Sexual dysfunction is common in endometrial cancer survivors (ECS). Our group previously tested a six-month exercise intervention in ECS. We performed a secondary analysis to determine intervention's impact on sexual health. Methods We studied 100 post-treatment Stage I-IIIa sedentary ECS who participated in a non-controlled, single-arm, home-based exercise intervention utilizing telephone counseling, printed material, and pedometers. Quality-of-life and physical activity measures were collected at baseline and six months. Sexual function (SF) and sexual interest (SI) scores were extracted from the QLACS questionnaire. Results Baseline SF and SI were lower in survivors with less than a four-year college degree (P < 0.001). Baseline SI was higher in survivors who were married or living with a significant other (P = 0.012). No significant differences in SF or SI were observed based on obesity status, race, time since diagnosis, or treatment type. Post-intervention, mean SF score improved (P = 0.002), 51% of participants had improved SI, and 43% had improved SF. When controlled for age and time since diagnosis, a one-hour increase in weekly physical activity was associated with a 6.5% increased likelihood of improved SI (P = 0.04). Increased physical activity was not associated with improved SF. Conclusions Although causation cannot be determined in this study, the correlation between receipt of an exercise intervention and improved sexual health for ECS is a novel finding. This finding suggests a role for physical activity as a strategy to improve the sexual health of ECS, which our group is examining in a larger prospective study.

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