AS518 - A pilot RNA-seq study among Long Life Study participants of the WHI

Investigator Names and Contact Information

Themistocles (Tim) Assimes (tassimes@stanford.edu)

Introduction/Intent

Improved understanding of the pathophysiology and risk prediction of complex traits will not occur without the identification of a large number of novel susceptibility biomarkers from orthogonal sources followed by the thoughtful incorporation of these biomarkers into current risk prediction algorithms (i.e. the multi-marker approach). Over the last decade, major technological advances have been made which now allow us to reliably and comprehensively assay a variety of intracellular and extracellular biologic markers including those related to DNA, RNA, and proteins.

The overall goal of this research program is to produce the highest quality gene expression profiles possible from whole blood RNA collected during the Long Life Study (LLS) and to integrate these data with existing clinical, biomarker, and genetic data, as well additional "omic" data. We anticipate that such integration will provide the WHI and larger scientific community with a valuable tool to better understand the pathophysiology of diverse traits, and an improved ability to develop and deploy approaches that predict future morbidity and mortality in elderly women.

The investigative team includes specialists in clinical medicine, epidemiology, bioinformatics, biostatistics, laboratory science, and genetics. The team has extensive experience in translational research. Importantly, the team includes a recently appointed faculty member at Stanford with extensive experience generating and integrating gene expression data using various high throughput technologies including RNA-seq. Thus, we are confident that the goals of this study are achievable

Specific Aims

Aim 1: Create cDNA libraries for 100 aliquots of 0.5ug of whole blood RNA from 100 African American participants of the WHI LLS.

Aim 2: Sequence these cDNA libraries to a depth of 32.5 million reads / sample.

Aim 3: Quantify transcript expression and compare discovered expression quantitative trait loci to the Genotyping-tissue expression project (GTEx), The SardiNIA Project, and Depression, Genes and Network (DGN) cohorts.