Cardiometabolic Disease Epidemiology

Common Genetic Variation and Quantitative Diabetes Traits

PI: Kabagambe, E. K.   Funding Agency: NCI  Grant No.: R01 DK78616 
In this study we seek to identify novel diabetes susceptibility genes in African American men and women and to determine whether genetic loci associated with type 2 diabetes in European Americans are transferable to African Americans. This work is done through the African American Glucose and Insulin Genetic Epidemiology (AAGILE) Consortium which includes data from over 16 cohorts and various electronic medical records including BioVU.

Consortium Study of Modifiable Causes of Death in Asians
PI:  Zheng, WeiPotter, John    Funding Agency: NCI      Grant No.:  R03 CA153116 
In Asian countries, in the wake of lifestyle changes (reduced physical activity, increased prevalence of obesity and cigarette smoking, and heavy alcohol consumption), the burden of chronic diseases has increased substantially in recent decades. Each of these modifiable factors has been linked to premature death; however, the overall impact of these factors on total and cause-specific mortality is unclear. This study will also evaluate the association of central obesity with total and cause-specific mortality. This study is being conducted as part of the Asia Cohort Consortium, in which data from more than 1 million individuals recruited in approximately 20 cohort studies have been harmonized and analyzed to quantify the association of BMI and tobacco smoking with total and cause-specific mortality (Zheng W, et al, NEJM, 2011; 364(8):719-29; Zheng W, et al, PLoS Medicine, 2014; 11(4):e1001631). Study results will inform the design of effective programs tackling the emerging epidemic of chronic diseases and reduce premature death in Asian countries.

Fatty acid desaturase activity, fish oil and colorectal cancer chemoprevention 
PI: Murff, Harvey       Funding Agency: NCI       Grant No.: R01 CA160938 
Description: Observational studies have suggested that the n-3 polyunsaturated fatty acids, eicosapentanoic acid and docosahexanoic acid, may reduce the risk of colorectal cancer. Our hypothesis is that individuals with lower activity of fatty acid desaturase-1(FADS1) will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity due to lower production of endogenous arachidonic acid. To test this hypothesis we will recruit 150 participants and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. Our first factor will be FADS1 genotype (GG, GT, and TT) and our second factor will be fish oil supplementation (fish oil versus placebo). Our specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention.
Fogarty International Clinical Research Scholars Support Center @ Vanderbilt-AAMC (FICRSF)
PI: Vermund, Sten        Funding Agency: FIC               Grant No.:  R24 TW007988 
Description: The goal of the program is to help train and inspire both US and foreign graduate students in research techniques and topic areas applicable to resource-limited and/or tropical countries.

Metabolite profiles and the risk of diabetes in Asians 
PI: Wang, Thomas: Shu, Xiao-OU; Gerzten, Robert (Harvard University)  Funding Agency: NIH/NIDDK  
Grant No.:  1R01DK108159-01A1
Description:Type 2 diabetes mellitus (DM) is a major cause of morbidity and mortality worldwide. The pathogenesis of DM reflects a complex interplay of genetic, dietary, and environmental exposures affecting multiple pathways. It is also increasingly recognized that there is phenotypic heterogeneity among individuals who develop DM. Using the resources from the Shanghai Women’s Health Study and Shanghai Men’s Health Study, this study comprehensively evaluates metabolomic profiling to identify metabolites associated with incident DM in a population with low prevalence of diabetes. This research includes a nested case-control study and a separate case-cohort study to replicate findings, as well as an assessment of whether the addition of metabolites improves the ability to predict the risk of DM in Asians, compared with risk factors alone, and whether the metabolite predictors are associated with mortality and cardiovascular events.


Obesity, Inflammation, and BPH 
PI: Fowke, Jay H.       Funding Agency:  NIDDK           Grant No.: R01 DK087962 
Description: The purpose of the study is to investigate the relationship between obesity and BPH.  Obesity generates a state of chronic systemic inflammation known to enhance arthrosclerosis, diabetes, and other inflammatory diseases. Several studies also suggest that obese men are also more likely to develop lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH).  However, much of the epidemiologic evidence relies on self-reported BPH outcomes, and there are few, if any, animal models to characterize the obesity-BPH relationship. Thus, our long-term goals are to characterize the relationship between obesity and prostate tissue inflammation and hyperplasia, investigate potential mechanisms by which obesity advances BPH, develop a mouse model of BPH for mechanistic studies, and to conduct a prospective epidemiologic study to investigate the clinical impact of obesity on BPH progression.
O’Brien Center Development: BPH and Obesity 
PI: Fowke, Jay H.       Funding Agency:   NIDDK                Grant No.: P20 DK097782
Description: This is toward development of a Center to investigate obesity and BPH.  we conduct two epidemiologic investigations to determine if prostate tissue inflammation or LUTS severity is associated with hypothesized pathways linking obesity to BPH, including increased PGE-M (inflammation), F2-isoprostanes (oxidative stress), and adiponectin and C-peptide (insulin activity).
Shanghai Men’s Health Study (SMHS) 
PI: Shu, Xiao Ou      Funding Agency: NCI       Grant No.: R01 CA82729, UM1 CA173640 
Description: The Shanghai Men’s Health Study (SMHS), funded by NCI since 2001, is a population-based cohort study of 61,482 men aged between 35 and 75 years and recruited from 2002 to 2006. At baseline, detailed information on dietary intakes, personal habits, occupational history, medical history, and other lifestyle factors was collected, and anthropometrics were measured. Blood or buccal cell, and  urine samples were collected from 89% of participants. The cohort has been followed through multiple in-person surveys to update exposure information and through record linkages with the population-based Shanghai Cancer Registry and Shanghai Vital Statistics Registry to obtain information on cancer occurrence and survival status. Over the years, SMHS data and biological samples have been used to evaluate many important etiologic hypotheses addressing the contributions of environmental, dietary, lifestyle, and genetic exposures to the development of cancer and other chronic diseases. The cohort supports multiple studies, including over 25 consortium projects.
Shanghai Women's Health Study (SWHS)
PI: Zheng, Wei          Funding Agency: NCI        Grant No.:  UM1 CA182910 
Description:  This population-based prospective cohort study was initiated in 1996. From 1996 to 2000, approximately 75,000 Chinese women living in Shanghai were recruited into the study. In addition to survey data, most study participants donated blood (75%) and urine (87%) samples at baseline. Approximately 50% of study participants who did not donate a blood sample provided a sample of exfoliated buccal cells. This cohort of women is being followed for incidence of site-specific cancers and cause-specific mortality through a combination of in-person surveys and record linkages with population-based registries. Four in-person follow-up surveys have been completed, each with a response rate greater than 90%. The resources from this study have supported multiple studies, including approximately 40 international research consortia, to address etiologic hypotheses for cancers and other chronic diseases. The SWHS, with its large sample size, wealth of resources, and unique exposure patterns and disease spectrum, provides exceptional opportunities to address many significant hypotheses that cannot be adequately investigated in other existing cohorts.

Treatment Intensification in Type 2 Diabetes Mellitus
PI: Griffin, Marie     Funding Agency:  AHRQ  Grant No.: HHSAA2902010000161 DEcIDE 2, TO2
This project uses VA national data to address the comparative effectiveness of specific DM treatments in reducing cardiovascular or kidney disease.

Vanderbilt-Emory-Cornell-Duke Consortium for Global Health Fellows (VECDor) 
PI: Vermund, StenHeimburger, Douglas  Funding Agency: FIC      Grant No.: R25 TW009337 
Description: This project aims to nurture a new generation of global health researchers through a collaborative training program with overseas research institutions from low and middle-income countries with which our universities have worked for decades.
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Vanderbilt-Shanghai Chronic Disease Research Training Program (VU-Shanghai CDRTP) 
PI: Shu, Xiao Ou      Funding Agency:  FIC           Grant No.: D43 TW008313 
Description: The Vanderbilt-Shanghai Chronic Disease Research Training Program, funded by the NIH Fogarty International Center, aims to train a new generation of scientists and future leaders in chronic disease research in China and equip them with the expertise to conduct multi-disciplinary chronic disease research and build research and training capacity, as well as establish long-term international collaborative partnerships in chronic disease research and prevention. The training program includes the organization of two workshops and an international conference on chronic disease research and prevention in China and the training of 18 medium-term (6-month) and long-term (12-month) visiting fellows at the Vanderbilt Epidemiology Center. The program primarily focuses on advanced training in epidemiological and biostatistical methodology, design and execution of multidisciplinary research projects, and building expertise in cancer, cardiovascular disease, and diabetes research, as well as grant writing skills.
Vanderbilt Training Program in Molecular and Genetic Epidemiology of Cancer (MAGEC
PI: Shu, Xiao OuHeimburger, Douglas    Funding Agency: NIC         Grant No.: R25 CA160056 
Description: This program is designed to address the urgent need to build an elite class of epidemiologists to lead the new era of multidisciplinary collaborative research in cancer by delivering individualized didactic and research training to equip postdoctoral fellows from a variety of disciplines with the methodological tools, practical laboratory and survey-research knowledge, and hands-on research and grant writing experience necessary to launch independent careers in the molecular and genetic epidemiology of cancer.