DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content

Lactose provides an easily-digested energy source for neonate mammals, and is the primary carbohydrate in milk. Lactose is also a key component of many human food products, though compared to analyses of other milk components, the genetic control of lactose has been little studied. Here we present the first GWAS of milk lactose concentration and yield, investigated in a population of 12,000 taurine dairy cattle. We detail 27 QTL spanning these traits, and subsequently validate the effects of 26 of these loci in a separate population of 18,000 cows. We next present data implicating causative genes and variants for these QTL. Fine mapping of these regions using imputed, whole genome sequence-resolution genotypes reveals protein-coding candidate causative variants affecting the ABCG2, DGAT1, STAT5B, KCNH4, NPFFR2 and RNF214 genes. Eleven of the remaining QTL appear to be driven by regulatory effects, suggested by the presence of co-locating, co-segregating eQTL discovered using mammary RNA..., LC_GWAS_results.txtGWAS of lactose concentration in 12k cows, using a generalised least squares model to account for pedigree.LY_GWAS_results.txtGWAS of lactose yield in 12k cows, using a generalised least squares model to account for pedigree.imputed_seq_results_22loci-LC.txtAssociations for 1Mbp windows of imputed whole genome sequence around 5 GWAS peaks for lactose concentration, using GLS to account for pedigree.imputed_seq_results_5loci-LY.txtAssociations for 1Mbp windows of imputed whole genome sequence around 5 GWAS peaks for lactose yield, using GLS to account for pedigree.eQTL for genes at lactose QTL peaks1Mbp cis-eQTL from imputed whole-genome sequence for 313 genes arounds QTL peaks for lactose phenotypes. Calculated using GLS to account for pedigree.all-eQTL-seq-model-outputs.zipimputed-seq-genotypes-Chr1.153640000-154640000.vcfImputed genotypes for variants within 1Mbp of the Chr1:153.96 LC QTL, for 357 animals.imputed-seq-genotypes-Chr2.127140000-128140000.vcfImputed gen...,