TY - UNPB
T1 - Evaluation of Bayesian Linear Regression Derived Gene Set Test Methods
AU - Bai, Zhonghao
AU - Gholipourshahraki, Tahereh
AU - Shrestha, Merina
AU - Hjelholt, Astrid
AU - Kjølby, Mads
AU - Rohde, Palle Duun
AU - Sørensen, Peter
PY - 2024/2/25
Y1 - 2024/2/25
N2 - Gene set tests can pinpoint genes and biological pathways that exert small to moderate effects on complex diseases like Type 2 Diabetes (T2D). By aggregating genetic markers based on biological information, these tests can enhance the statistical power needed to detect genetic associations. Our goal was to develop a gene set test utilizing Bayesian Linear Regression (BLR) models, which account for both linkage disequilibrium (LD) and the complex genetic architectures intrinsic to diseases, thereby increasing the detection power of genetic associations. Through a series of simulation studies, we demonstrated how the efficacy of BLR derived gene set tests is influenced by several factors, including the proportion of causal markers, the size of gene sets, the percentage of genetic variance explained by the gene set, and the genetic architecture of the traits. Comparing our method with other approaches, such as the gold standard MAGMA (Multi-marker Analysis of Genomic Annotation) approach, our BLR gene set test showed superior performance. This suggests that our BLR-based approach could more accurately identify genes and biological pathways underlying complex diseases.
AB - Gene set tests can pinpoint genes and biological pathways that exert small to moderate effects on complex diseases like Type 2 Diabetes (T2D). By aggregating genetic markers based on biological information, these tests can enhance the statistical power needed to detect genetic associations. Our goal was to develop a gene set test utilizing Bayesian Linear Regression (BLR) models, which account for both linkage disequilibrium (LD) and the complex genetic architectures intrinsic to diseases, thereby increasing the detection power of genetic associations. Through a series of simulation studies, we demonstrated how the efficacy of BLR derived gene set tests is influenced by several factors, including the proportion of causal markers, the size of gene sets, the percentage of genetic variance explained by the gene set, and the genetic architecture of the traits. Comparing our method with other approaches, such as the gold standard MAGMA (Multi-marker Analysis of Genomic Annotation) approach, our BLR gene set test showed superior performance. This suggests that our BLR-based approach could more accurately identify genes and biological pathways underlying complex diseases.
U2 - 10.1101/2024.02.23.581726
DO - 10.1101/2024.02.23.581726
M3 - Preprint
SP - 1
EP - 31
BT - Evaluation of Bayesian Linear Regression Derived Gene Set Test Methods
PB - bioRxiv
ER -