Back

Inferring a directed acyclic graph of phenotypes from GWAS summary statistics

Zilinskas, R.; Li, C.; Shen, X.; Pan, W.; Yang, T.

2023-02-11 molecular biology
10.1101/2023.02.10.528092 bioRxiv
Show abstract

SO_SCPLOWUMMARYC_SCPLOWEstimating phenotype networks is a growing field in computational biology. It deepens the understanding of disease etiology and is useful in many applications. In this study, we present a method that constructs a phenotype network by assuming a Gaussian linear structure model embedding a directed acyclic graph (DAG). We utilize genetic variants as instrumental variables and show how our method only requires access to summary statistics from a genome-wide association study (GWAS) and a reference panel of genotype data. Besides estimation, a distinct feature of the method is its summary statistics-based likelihood ratio test on directed edges. We applied our method to estimate a causal network of 29 cardiovascular-related proteins and linked the estimated network to Alzheimers disease (AD). A simulation study was conducted to demonstrate the effectiveness of this method. An R package sumdag implementing the proposed method, all relevant code, and a Shiny application are available at https://github.com/chunlinli/sumdag.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.