ArticleProceedings of the National Academy of Sciences of the United States of America2010
Association weight matrix for the genetic dissection of puberty in beef cattle.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58 citing papers in PubMed, 173 citations in OpenAlex.
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- A gene co-association network regulating gut microbial communities in a Duroc pig population.Microbiome · 2021Article
- A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs.Frontiers in immunology · 2021Article
- A systems biology framework integrating GWAS and RNA-seq to shed light on the molecular basis of sperm quality in swine.Genetics, selection, evolution : GSE · 2020Article
- Gene networks for three feed efficiency criteria reveal shared and specific biological processes.Genetics, selection, evolution : GSE · 2020Article
- Identification and Functional Annotation of Genes Related to Horses' Performance: From GWAS to Post-GWAS.Animals : an open access journal from MDPI · 2020Article
- Dynamics of genomic architecture during composite breed development in cattle.Animal genetics · 2020Article
- Common Gene Modules Identified for Chicken Adiposity by Network Construction and Comparison.Frontiers in genetics · 2020Article
- Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries).Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- Integrating genome-wide co-association and gene expression to identify putative regulators and predictors of feed efficiency in pigs.Genetics, selection, evolution : GSE · 2019Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We describe a systems biology approach for the genetic dissection of complex traits based on applying gene network theory to the results from genome-wide associations. The associations of single-nucleotide polymorphisms (SNP) that were individually associated with a primary phenotype of interest, age at puberty in our study, were explored across 22 related traits. Genomic regions were surveyed for genes harboring the selected SNP. As a result, an association weight matrix (AWM) was constructed with as many rows as genes and as many columns as traits. Each {i, j} cell value in the AWM corresponds to the z-score normalized additive effect of the ith gene (via its neighboring SNP) on the jth trait. Columnwise, the AWM recovered the genetic correlations estimated via pedigree-based restricted maximum-likelihood methods. Rowwise, a combination of hierarchical clustering, gene network, and pathway analyses identified genetic drivers that would have been missed by standard genome-wide association studies. Finally, the promoter regions of the AWM-predicted targets of three key transcription factors (TFs), estrogen-related receptor gamma (ESRRG), Pal3 motif, bound by a PPAR-gamma homodimer, IR3 sites (PPARG), and Prophet of Pit 1, PROP paired-like homeobox 1 (PROP1), were surveyed to identify binding sites corresponding to those TFs. Applied to our case, the AWM results recapitulate the known biology of puberty, captured experimentally validated binding sites, and identified candidate genes and gene-gene interactions for further investigation.
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