title: Genetic dissection of blood lipid traits by integrating genome-wide association study and gene expression profiling in a porcine model.
abstract: BACKGROUND
  Serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) are highly heritable traits that are used clinically to evaluate risk for cardiovascular disease in humans. In this study, we applied a genome-wide association study (GWAS) in 1,075 pigs from two populations and gene expression studies on 497 liver samples to dissect the genetic basis of serum lipids in a pig model.
  
  
  RESULTS
  We totally identified 8, 5, 2 and 3 genomic loci harboring 109 SNPs that were significantly associated with LDL-C, TC, TG and the ratio of HDL-C/LDL-C in two experimental populations, respectively. In the F2 population, the most prominent SNP was identified at the SSC3: 124,769,847 bp where APOB is the well-known candidate gene. However, in the Sutai population, the most number of significant SNPs was identified at SSC2: 64.97-82.22 Mb where LDLR was identified as the candidate gene. Furthermore, we firstly reported 4 novel genomic loci in pigs harboring the LDL-C-associated SNPs. We also observed obvious population heterogeneity in the two tested populations. Through whole-genome gene expression analysis, we detected 718 trait-correlated expressions. Many of these transcripts correspond to candidate genes for blood lipids in humans. The GWAS mapped 120 cis-eQTLs and 523 trans-eQTLs for these transcripts. One gene encoding the transcript gnl|UG|Ssc#S35330332 stands out to be an important candidate gene for LDL-C by an integrative analysis of GWAS, eQTL and trait-associated expression.
  
  
  CONCLUSIONS
  We identified the genomic regions or candidate genes associated with blood lipids by an integrative analysis of GWAS, QTT and eQTL mapping in pigs. The findings would benefit the further identification of the causative genes for blood lipid traits in both pigs and humans.
authors.affiliation: Key Laboratory for Animal Biotechnology of Jiangxi Province and the Ministry of Agriculture of China, Jiangxi Agricultural University, 330045, Nanchang, China. lushenghuang@hotmail.com.
authors.forename: Congying
authors.initials: C
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zeng
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Chenlong
authors.initials: C
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Lusheng
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D034421:Sus scrofa; D059467:Transcriptome
chemical_list: D008055:Lipids