Identifying causal variants and genes using functional genomics in specialized cell types and contexts.

TitleIdentifying causal variants and genes using functional genomics in specialized cell types and contexts.
Publication TypeJournal Article
Year of Publication2020
AuthorsLiu, B, Montgomery, SB
JournalHum Genet
Volume139
Issue1
Pagination95-102
Date Published2020 Jan
ISSN1432-1203
Abstract

A central goal in human genetics is the identification of variants and genes that influence the risk of polygenic diseases. In the past decade, genome-wide association studies (GWAS) have identified tens of thousands of genetic loci associated with various diseases. Since the majority of such loci lie within non-coding regions and have many candidate variants in linkage disequilibrium, it has been challenging to accurately identify specific causal variants and genes. To aid in their discovery a variety of statistical and experimental approaches have been developed. These approaches often borrow information from functional genomics assays such as ATAC-seq, ChIP-seq and RNA-seq to annotate functional variants and identify regulatory relationships between variants and genes. While such approaches are powerful, given the diversity of cell types and environments, it is paramount to select disease-relevant contexts for follow-up analyses. In this review, we discuss the latest developments, challenges, and best practices for determining the causal mechanisms of polygenic disease risk variants with functional genomics data from specialized cell types.

DOI10.1007/s00439-019-02044-2
Alternate JournalHum. Genet.
PubMed ID31317254
PubMed Central IDPMC6942616
Grant ListU01 HG009431 / HG / NHGRI NIH HHS / United States
R01 HG008150 / HG / NHGRI NIH HHS / United States
R01HG008150 / NH / NIH HHS / United States
R01 HL142015 / HL / NHLBI NIH HHS / United States
R33 HL120757 / HL / NHLBI NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States