One of the central problems in human genetics is to understand the molecular basis of complex disease. Of the millions of DNA positions that vary among humans, which sites actually impact human phenotypes and disease? It is now clear that an enormous number of variants across the genome affect any given complex trait. In recent work we have proposed that these most of these variants affect disease risk by acting as trans-regulators of core disease genes. However at present we have very little knowledge of trans-regulatory networks, and traditional trans-eQTL mapping is underpowered even with thousands of samples. In this project we propose to implement a CRISPR-based screening approaching for measuring trans-regulators of genes of interest in primary T cells. We will evaluate the strength of this approach as an experimental alternative to trans-eQTL mapping.

Public Health Relevance

The purpose of this project is to develop a new experimental and computational approach to identifying trans-regulators for genes/proteins of interest. We anticipate that this technique could provide a powerful and affordable alternative to trans-eQTL mapping, and should be extremely valuable for interpreting GWAS data.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
3R01HG008140-03S1
Application #
9694854
Study Section
Special Emphasis Panel (ZHG1)
Program Officer
Brooks, Lisa
Project Start
2016-06-23
Project End
2019-05-31
Budget Start
2018-09-19
Budget End
2019-05-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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