Evidence map›Paper›PMID 39716056›Full record

ArticleBMC genomics2024

Evaluation of Bayesian Linear Regression derived gene set test methods.

Zhonghao Bai, Tahereh Gholipourshahraki, Merina Shrestha, Astrid Hjelholt, Sile Hu, Mads Kjolby, Palle Duun Rohde, Peter Sørensen

Abstract read
In one paragraph

Article in BMC genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Zhonghao BaiCenter for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark. zhonghao.bai@qgg.au.dk.
Tahereh GholipourshahrakiCenter for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
Merina ShresthaCenter for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
Astrid HjelholtDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Sile HuHuman Genetics Centre of Excellence, Novo Nordisk Research Centre Oxford, Oxford, UK.
Mads KjolbyDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Palle Duun RohdeGenomic Medicine, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Peter SørensenCenter for Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark. pso@qgg.au.dk.

Funding

Novo Nordisk Fonden NNF20SA0061466
6 · The paper itself

Abstract

backgroundGene 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.

resultsOur 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. By using KEGG pathways, eQTLs, and regulatory elements as different kinds of gene sets with T2D results, we also assessed the performance of gene set tests in explaining more about real phenotypes.

conclusionsComparing 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. Combining performance of our method in simulated and real phenotypes, this suggests that our BLR-based approach could more accurately identify genes and biological pathways underlying complex diseases.

Indexed as

Bayes TheoremDiabetes Mellitus, Type 2Linkage DisequilibriumComputer SimulationGenome-Wide Association StudyHumansLinear ModelsModels, GeneticPhenotypeQuantitative Trait LociBLRComplex diseaseGene set testType 2 diabetes

Identifiers

PMID39716056
PMCPMC11667926

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.