Regulatory and coding genome regions are enriched for trait associated variants in dairy and beef cattle

Koufariotis, Lambros, Chen, Yi-Ping Phoebe, Bolormaa, Sunduimijid and Hayes, Ben J. (2014) Regulatory and coding genome regions are enriched for trait associated variants in dairy and beef cattle. BMC Genomics, 15 . doi:10.1186/1471-2164-15-436


Author Koufariotis, Lambros
Chen, Yi-Ping Phoebe
Bolormaa, Sunduimijid
Hayes, Ben J.
Title Regulatory and coding genome regions are enriched for trait associated variants in dairy and beef cattle
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2014-06-06
Sub-type Article (original research)
DOI 10.1186/1471-2164-15-436
Open Access Status DOI
Volume 15
Total pages 16
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: In livestock, as in humans, the number of genetic variants that can be tested for association with complex quantitative traits, or used in genomic predictions, is increasing exponentially as whole genome sequencing becomes more common. The power to identify variants associated with traits, particularly those of small effects, could be increased if certain regions of the genome were known a priori to be enriched for associations. Here, we investigate whether twelve genomic annotation classes were enriched or depleted for significant associations in genome wide association studies for complex traits in beef and dairy cattle. We also describe a variance component approach to determine the proportion of genetic variance captured by each annotation class.
Results: P-values from large GWAS using 700K SNP in both dairy and beef cattle were available for 11 and 10 traits respectively. We found significant enrichment for trait associated variants (SNP significant in the GWAS) in the missense class along with regions 5 kilobases upstream and downstream of coding genes. We found that the non-coding conserved regions (across mammals) were not enriched for trait associated variants. The results from the enrichment or depletion analysis were not in complete agreement with the results from variance component analysis, where the missense and synonymous classes gave the greatest increase in variance explained, while the upstream and downstream classes showed a more modest increase in the variance explained.
Conclusion: Our results indicate that functional annotations could assist in prioritization of variants to a subset more likely to be associated with complex traits; including missense variants, and upstream and downstream regions. The differences in two sets of results (GWAS enrichment depletion versus variance component approaches) might be explained by the fact that the variance component approach has greater power to capture the cumulative effect of mutations of small effect, while the enrichment or depletion approach only captures the variants that are significant in GWAS, which is restricted to a limited number of common variants of moderate effects.
Keyword Enrichment depletion
GWAS prioritization
Regulatory genome
Variants component analysis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article number 436

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Alliance for Agriculture and Food Innovation
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 12 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 05 Aug 2016, 09:50:07 EST by System User on behalf of Learning and Research Services (UQ Library)