RatXcan: A framework for cross-species integration of genome-wide association and gene expression data
Natasha Santhanam, Sandra Sanchez-Roige, Sabrina Mi, Yanyu Liang, Apurva S. Chitre, Daniel Munro, Denghui Chen, Jianjun Gao, Angel Garcia-Martinez, Anthony M. George, Alexander F. Gileta, Wenyan Han, Katie Holl, Alesa Hughson, Christopher P. King, Alexander C. Lamparelli
TL;DR
RatXcan is a new method that helps link genetic data to gene expression in rats, making it easier to find shared biological patterns with humans.
Contribution
RatXcan extends transcriptome-wide association methods to account for genetic relatedness in rat models.
Findings
RatXcan identifies gene expression associations in rats while correcting for genetic relatedness.
Cis genetic architecture of gene expression is similar between rats and humans in brain tissues.
Genes linked to body length and BMI show significant overlap between rats and humans.
Abstract
Genome-wide association studies (GWAS) have implicated specific alleles and genes as risk factors for numerous complex traits. However, translating GWAS results into biologically and therapeutically meaningful discoveries remains extremely challenging. Most GWAS results identify noncoding regions of the genome, suggesting that differences in gene regulation are the major driver of trait variability. To better integrate GWAS results with gene regulatory polymorphisms, we previously developed PrediXcan (also known as “transcriptome-wide association studies” or TWAS), which maps SNPs to predicted gene expression using GWAS data. In this study, we developed RatXcan, a framework that extends this methodology to outbred heterogeneous stock (HS) rats. RatXcan accounts for the close familial relationships among HS rats by modeling the relatedness with a random effect that encodes the genetic…
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Taxonomy
TopicsGenetic Mapping and Diversity in Plants and Animals · Genetic Associations and Epidemiology · Genetic and phenotypic traits in livestock