A spectral framework to map QTLs affecting joint differential networks of gene co-expression.
Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype → expression → phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the cri...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-04-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1012953 |
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| Summary: | Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype → expression → phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype → network → phenotype mechanism. Here, we develop a network-based method, called spectral network quantitative trait loci analysis (snQTL), to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries. |
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| ISSN: | 1553-734X 1553-7358 |