Independent Research: Methodology, Family/Genetic Studies and Multicenter Studies

The Division of Biostatistics undertakes independent research by developing novel methods of analysis as well as by conducting substantive disease-related data analysis using state-of-the art methods. These research efforts are largely supported by NIH grants (R01’s, R21’s, U01’s etc).

The Division also plays leading roles in several multi-center family and genetic studies and multi-center clinical trials by serving either as a Coordinating Center CC) or a Data Coordinating Center (DCC). Genetic studies involve recruitment of families, collection of phenotypic data as well as the collection and analysis of genotypic data. Clinical trials studies involve the recruitment of subject who participate in a clinical intervention.

As a CC or DCC, the division assists the project by developing a central data entry and management system, checking the data for errors, tracking recruitment and publications, developing and producing reports for the Steering Committee, NIH, and a Monitoring Board, and analyzing the data collected and publishing the results. In addition to the above, as a Coordinating Center, the division is also responsible for a number of administrative tasks that include taking and distributing minutes from each meeting and conference call, and the development of the study Manual of Procedures.

Independent research grants in the Division of Biostatistics.

Functional GWAS for LVH Using IPS-Derived Cardiomyocytes:  The HyperGEN CIPS Study

Charles Gu, Subcontract PI
This project will use human induced pluripotent stem-cell (iPSC) technology to investigate and understand mechanisms and pathways underlying the genetic basis of Left Ventricular Hypertrophy (LVH) as a common and major risk factor for cardiovascular disease. We will derive iPSCs and ventricular cardiomyocytes to study the molecular changes associated with the development of LVH, by analyzing changes in gene expression under various conditions and perform family-based expression Quantitative Trait Loci (eQTL) analysis to study the impact of DNA variations on the molecular changes.

Genetics of Cardiomyocyte and Cardiac Matrix Interaction: The HyperGEN IPSC Study

Charles Gu, Subcontract PI
The interaction between the cardiac matrix and cardiomyocytes plays an important role in the development of Left Ventricular Hypertrophy. We propose to study these mechanisms and identify genetic markers using human induced pluripotent stem cell drived cardiomyocytes. Improving our understanding of these mechanisms can lead to novel treatment options and methods to identify individuals at increased risk.

HyperGEN: Genetics of Left Ventricular Hypertrophy

DC Rao, Subcontract PI
This study seeks to discover which genetic factors may cause an enlarged heart; this may ultimately lead to new diagnoses and treatments to help lower cardiovascular disease risk in blacks.

Rare Variants for Hypertension in Taiwan Chinese

DC Rao, PI
The primary goal of the proposed research is to identify rare and low frequency variants that have large effects on blood pressure and hypertension by carrying out exome sequencing in 150 highly enriched Taiwan Chinese sib-pairs (300 subjects) and 300 unrelated controls, then to validate the top 6,000 SNPs in larger samples, and finally replicate the top 50 SNPs in nearly 45,000 multi-ethnic subjects.

A Multi-Ethnic Study of Gene-Lifestyle Interactions in Cardiovascular Traits

DC Rao, PI
The primary goal of the proposed research is to leverage existing GWAS and Exome Chip data in 25 large multi-ethnic cohorts to discover additional genetic loci for cardiovascular traits by modeling gene-lifestyle interactions, using pleiotropy analysis of correlated traits, and pathway analysis. The investigation will be carried out in 150,765 samples of European Americans, African Americans, Hispanic Americans, and Asians. Approximately equal sample sizes will be used for replication.

PRIDE Summer Institute in Cardiovascular Genetic Epidemiology

DC Rao, PI
Training and mentoring a diverse biomedical research workforce in state-of-the-art approaches to research in cardiovascular diseases is of considerable public health importance. A highly desirable added benefit is that the trained scientists are more likely to succeed in their research efforts to deal with health disparities among racial and ethnic groups.

PRIDE Coordination Center

Treva K Rice, PI
The PRIDE is a mentored summer training experience in developing research skills for junior-level faculty who are underrepresented in the biomedical sciences. The Coordination Core will track indices of career success (e.g. grant awards) over time to determine if these mentored training programs will lead to increasing the diversity among individuals engaged in health related research.

Data Analysis and Coordinating Center (DACC) for Research Training Activities

Treva K Rice, PI
This Data Analysis and Coordination Center (DACC) will track and evaluate the education and career progress of trainees from over 50 NHGRI-funded research training programs.  The overall project focus is on increasing the persistence of students in science, technology, engineering, and mathematics (STEM) fields, and particularly on increasing the successful participation of students from diverse backgrounds in genomics and Ethical, Legal, and Social Issues (ELSI) research.  This focus is consistent with the trans-NIH effort to promote diversity in the biomedical research workforce so that, by increasing the diversity of researchers’ perspectives and ideas, health problems that disproportionately affect minority populations may be better addressed.

The Effectiveness of Family-based Weight Loss Treatment Implemented in Primary Care – DCC

Ken Schechtman, PI
The proposed research is designed to translate an evidence-based family-based weight loss treatment for childhood obesity (FBT) into primary care settings using co-located interventionists to serve as a model for care delivered within a patient-centered medical home. FBT plus enhanced usual care (FBT+EUC) will be compared to enhanced usual care (EUC) alone, and the families will be followed for a 2 year period to assess between group differences in the targeted child and parent outcomes, weight changes in non-targeted siblings who are overweight/obese, parent and child changes in delay of gratification, and how these changes relate to weight loss, and the assessment of how provider attitudes predict their intention to use FBT in the future. The results of this study will inform future dissemination and implementation of FBT into primary care settings.

Massive Transfusion epidemiology and outcomes in children (MATIC) study

Ken Schechtman, MPI
The MATIC study is a multicenter, prospective, observational study that will collect data on approximately 502 pediatric patients at approximately 35 sites on all massive transfusion protocols (MTP) activations at participating centers over a two year period into an electronic database. The goal of this study is to determine indications, frequency, therapies used, and outcomes for children requiring MTP activation as well as to determine if early and sustained hemostatic resuscitation is associated with increased survival in children requiring MTP activation by analyzing the specific timing of each blood product transfused, as well as the ratios and deficits of plasma and platelets to RBCs.

Two Preclinical Latent Scores to Predict Occurrence of DAT

Chengjie Xiong, PI
This project will focus on detecting the earliest possible signs of preclinical cognitive and functional changes of Alzheimer’s disease.

Antecedent Biomarker Changes in AD: Ordering, Stages, and Implications for Trials

Chengjie Xiong, PI
This project proposes to analyze one of the world’s largest biomarker database with a crucial age window (~40 y to 65 y) that will capture the very initiation of major changes prior to the symptom onset of AD so that therapeutic interventions can be tested and allowed well before dementia symptoms are fully developed.