Genome Wide Association Study for Bovine Milk Cholesterol Content

Being considered a risk factor for several human diseases, cholesterol (CHL) has received enormous attention in recent years. Milk fat is the second contributor to daily dietary CHL intake. Therefore reducing CHL content in milk (fat) might be important to lower dietary CHL intake. This study aimed to identify single nucleotide polymorphisms (SNPs), candidate genes and biological pathways involved in regulating CHL content in milk via a genome wide association study (GWAS) and pathway analyses. Cholesterol contents (mg/100 g milk fat) of 1,528 cows were measured using gas chromatography. DNA from hair samples of cows was used for 50k SNP genotyping. After quality control, GWAS was performed with 1,486 cows and 44,364 SNPs using a univariate linear mixed model. The most important QTL for CHL was 2.5-2.7 Mb region on chromosome (Bta) 5 where the two most significant SNPs (BTB-02053074, P = 2.32e-05 and BTB-00214293, P = 1.50e-05) are located. Other important QTL regions were found on Bta 6 (55 and 90 Mb), 8 (88 Mb), 10 (71 Mb) and 21 (14 and 20 Mb). Important positional candidate genes included milk fat globule-EGF factor 8 protein (MFGE8), albumin (ALB) and several members of solute carrier family (SLC4A1, SLC1A3 and SLC16A7). Validation of identified QTL and further analyses, including a GWAS with more data (animals and genotypes), positional candidate genes enrichment, and confirmation of potential candidate genes may uncover bio-markers for selection of reduced milk CHL content and further improve the understanding of the genetic mechanisms underlying milk CHL content.