DOI: 10.5061/dryad.vv469
title: Data from: DNA and RNA-sequence based GWAS highlights membrane-transport genes as key modulators of milk lactose content

description: 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 sequence
 data representing a population of 357 lactating cows. Pathway analysis of
 genes representing all lactose-associated loci shows significant
 enrichment of genes located to the endoplasmic reticulum, with functions
 related to ion channel activity mediated through the LRRC8C, P2RX4, KCNJ2
 and ANKH genes. Together, these findings highlight novel candidate genes
 and variants involved in milk lactose regulation, whose impacts on
 facilitated and active membrane transport mechanisms reinforce the key
 osmo-regulatory roles of lactose in milk.
description: 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 genotypes for variants within 1Mbp of the Chr2:127.64 LC QTL, for 357 animals.imputed-seq-genotypes-Chr3.15020000-16020000.vcfImputed genotypes for variants within 1Mbp of the Chr3:15.52 LC QTL, for 357 animals.imputed-seq-genotypes-Chr3.53340000-54340000.vcfImputed genotypes for variants within 1Mbp of the Chr3:53.84 LC QTL, for 357 animals.imputed-seq-genotypes-Chr5.20640000-21640000.vcfImputed genotypes for variants within 1Mbp of the Chr5:21.14 LC QTL, for 357 animals.imputed-seq-genotypes-Chr5.31060000-32060000.vcfImputed genotypes for variants within 1Mbp of the Chr5:31.56 LC QTL, for 357 animals.imputed-seq-genotypes-Chr5.43660000-44660000.vcfImputed genotypes for variants within 1Mbp of the Chr5:44.16 LC QTL, for 357 animals.imputed-seq-genotypes-Chr5.93440000-94440000.vcfImputed genotypes for variants within 1Mbp of the Chr5:93.94 LY QTL, for 357 animals.imputed-seq-genotypes-Chr6.37260000-38260000.vcfImputed genotypes for variants within 1Mbp of the Chr6:37.76 LC QTL, for 357 animals.imputed-seq-genotypes-Chr6.88540000-89540000.vcfImputed genotypes for variants within 1Mbp of the Chr6:89.04 LC QTL, for 357 animals.imputed-seq-genotypes-Chr7.8270000-9270000.vcfImputed genotypes for variants within 1Mbp of the Chr7:8.77 LC QTL, for 357 animals.imputed-seq-genotypes-Chr10.1640000-2640000.vcfImputed genotypes for variants within 1Mbp of the Chr10:2.14 LC QTL, for 357 animals.imputed-seq-genotypes-Chr11.62950000-63950000.vcfImputed genotypes for variants within 1Mbp of the Chr11:63.45 LY QTL, for 357 animals.imputed-seq-genotypes-Chr14.1270000-2270000.vcfImputed genotypes for variants within 1Mbp of the Chr14:1.77 LY QTL, for 357 animals.imputed-seq-genotypes-Chr15.27860000-28860000.vcfImputed genotypes for variants within 1Mbp of the Chr15:28.36 LC QTL, for 357 animals.imputed-seq-genotypes-Chr16.24490000-25490000.vcfImputed genotypes for variants within 1Mbp of the Chr16:24.99 LC QTL, for 357 animals.imputed-seq-genotypes-Chr16.67270000-68270000.vcfImputed genotypes for variants within 1Mbp of the Chr16:67.77 LC QTL, for 357 animals.imputed-seq-genotypes-Chr17.55970000-56970000.vcfImputed genotypes for variants within 1Mbp of the Chr17:56.47 LC QTL, for 357 animals.imputed-seq-genotypes-Chr19.33010000-34010000.vcfImputed genotypes for variants within 1Mbp of the Chr19:33.51 LC QTL, for 357 animals.imputed-seq-genotypes-Chr19.42490000-43490000.vcfImputed genotypes for variants within 1Mbp of the Chr19:42.99 LC QTL, for 357 animals.imputed-seq-genotypes-Chr19.60630000-61630000.vcfImputed genotypes for variants within 1Mbp of the Chr19:61.13 LC QTL, for 357 animals.imputed-seq-genotypes-Chr20.31190000-32190000.vcfImputed genotypes for variants within 1Mbp of the Chr20:31.69 LY QTL, for 357 animals.imputed-seq-genotypes-Chr20.57950000-58950000.vcfImputed genotypes for variants within 1Mbp of the Chr20:58.45 LC QTL, for 357 animals.imputed-seq-genotypes-Chr26.22460000-23460000.vcfImputed genotypes for variants within 1Mbp of the Chr26:22.96 LY QTL, for 357 animals.imputed-seq-genotypes-Chr27.35710000-36710000.vcfImputed genotypes for variants within 1Mbp of the Chr27:36.21 LC QTL, for 357 animals.imputed-seq-genotypes-Chr28.6060000-7060000.vcfImputed genotypes for variants within 1Mbp of the Chr28:6.56 LC QTL, for 357 animals.imputed-seq-genotypes-Chr29.9110000-10110000.vcfImputed genotypes for variants within 1Mbp of the Chr29:9.61 LC QTL, for 357 animals.imputed-seq-genotypes-12k-Chr1.153640000-154640000.vcfImputed genotypes for variants within 1Mbp of the Chr1:154.14 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr1.153640000-154640000.vcf.gzimputed-seq-genotypes-12k-Chr2.127140000-128140000.vcfImputed genotypes for variants within 1Mbp of the Chr2:127.64 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr2.127140000-128140000.vcf.gzimputed-seq-genotypes-12k-Chr3.15020000-16020000.vcfImputed genotypes for variants within 1Mbp of the Chr3:15.52 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr3.15020000-16020000.vcf.gzimputed-seq-genotypes-12k-Chr3.53340000-54340000.vcfImputed genotypes for variants within 1Mbp of the Chr3:53.84 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr3.53340000-54340000.vcf.gzimputed-seq-genotypes-12k-Chr5.20640000-21640000.vcfImputed genotypes for variants within 1Mbp of the Chr5:21.14 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr5.20640000-21640000.vcf.gzimputed-seq-genotypes-12k-Chr5.31060000-32060000.vcfImputed genotypes for variants within 1Mbp of the Chr5:31.56 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr5.31060000-32060000.vcf.gzimputed-seq-genotypes-12k-Chr5.43660000-44660000.vcfImputed genotypes for variants within 1Mbp of the Chr5:44.16 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr5.43660000-44660000.vcf.gzimputed-seq-genotypes-12k-Chr5.93440000-94440000.vcfImputed genotypes for variants within 1Mbp of the Chr5:93.94 LY QTL, for 12,000 animals.imputed-seq-genotypes-Chr5.93440000-94440000.vcf.gzimputed-seq-genotypes-12k-Chr6.37260000-38260000.vcfImputed genotypes for variants within 1Mbp of the Chr6:37.76 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr6.37260000-38260000.vcf.gzimputed-seq-genotypes-12k-Chr6.88540000-89540000.vcfImputed genotypes for variants within 1Mbp of the Chr3:89.04 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr6.88540000-89540000.vcf.gzimputed-seq-genotypes-12k-Chr7.8270000-9270000.vcfImputed genotypes for variants within 1Mbp of the Chr7:8.77 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr7.8270000-9270000.vcf.gzimputed-seq-genotypes-12k-Chr10.1640000-2640000.vcfImputed genotypes for variants within 1Mbp of the Chr10:2.14 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr10.1640000-2640000.vcf.gzimputed-seq-genotypes-12k-Chr11.62950000-63950000.vcfImputed genotypes for variants within 1Mbp of the Chr11:63.45 LY QTL, for 12,000 animals.imputed-seq-genotypes-Chr11.62950000-63950000.vcf.gzimputed-seq-genotypes-Chr14.1270000-2270000.vcfImputed genotypes for variants within 1Mbp of the Chr14:1.77 LY QTL, for 12,000 animals.imputed-seq-genotypes-12k-Chr15.27860000-28860000.vcfImputed genotypes for variants within 1Mbp of the Chr15:28.36 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr15.27860000-28860000.vcf.gzimputed-seq-genotypes-12k-Chr16.24490000-25490000.vcfImputed genotypes for variants within 1Mbp of the Chr16:24.99 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr16.24490000-25490000.vcf.gzimputed-seq-genotypes-12k-Chr16.67270000-68270000.vcfImputed genotypes for variants within 1Mbp of the Chr16:67.77 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr16.67270000-68270000.vcf.gzimputed-seq-genotypes-12k-Chr17.55970000-56970000.vcfImputed genotypes for variants within 1Mbp of the Chr17:56.47 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr17.55970000-56970000.vcf.gzimputed-seq-genotypes-12k-Chr19.33010000-34010000.vcfImputed genotypes for variants within 1Mbp of the Chr19:33.51 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr19.33010000-34010000.vcf.gzimputed-seq-genotypes-12k-Chr19.42490000-43490000.vcfImputed genotypes for variants within 1Mbp of the Chr19:42.99 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr19.42490000-43490000.vcf.gzimputed-seq-genotypes-12k-Chr19.60630000-61630000.vcfImputed genotypes for variants within 1Mbp of the Chr19:61.13 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr19.60630000-61630000.vcf.gzimputed-seq-genotypes-12k-Chr20.31190000-32190000.vcfImputed genotypes for variants within 1Mbp of the Chr20:31.69 LY QTL, for 12,000 animals.imputed-seq-genotypes-Chr20.31190000-32190000.vcf.gzimputed-seq-genotypes-12k-Chr20.57950000-58950000.vcfImputed genotypes for variants within 1Mbp of the Chr20:58.45 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr20.57950000-58950000.vcf.gzimputed-seq-genotypes-Chr26.22460000-23460000.vcfImputed genotypes for variants within 1Mbp of the Chr26:22.96 LY QTL, for 12,000 animals.imputed-seq-genotypes-12k-Chr27.35710000-36710000.vcfImputed genotypes for variants within 1Mbp of the Chr27:36.21 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr27.35710000-36710000.vcf.gzimputed-seq-genotypes-12k-Chr28.6060000-7060000.vcfImputed genotypes for variants within 1Mbp of the Chr28:6.56 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr28.6060000-7060000.vcf.gzimputed-seq-genotypes-12k-Chr29.9110000-10110000.vcfImputed genotypes for variants within 1Mbp of the Chr29:9.61 LC QTL, for 12,000 animals.imputed-seq-genotypes-Chr29.9110000-10110000.vcf.gzHD-and-RNA-variants-Chr1.vcfAll HD and RNAseq variants on chromosome 1. Used in the paper for LC and LY GWAS.chr1.vcf.gzHD-and-RNA-variants-Chr2.vcfAll HD and RNAseq variants on chromosome 2. Used in the paper for LC and LY GWAS.chr2.vcf.gzHD-and-RNA-variants-Chr3.vcfAll HD and RNAseq variants on chromosome 3. Used in the paper for LC and LY GWAS.chr3.vcf.gzHD-and-RNA-variants-Chr4.vcfAll HD and RNAseq variants on chromosome 4. Used in the paper for LC and LY GWAS.chr4.vcf.gzHD-and-RNA-variants-Chr5.vcfAll HD and RNAseq variants on chromosome 5. Used in the paper for LC and LY GWAS.chr5.vcf.gzHD-and-RNA-variants-Chr6.vcfAll HD and RNAseq variants on chromosome 6. Used in the paper for LC and LY GWAS.chr6.vcf.gzHD-and-RNA-variants-Chr7.vcfAll HD and RNAseq variants on chromosome 7. Used in the paper for LC and LY GWAS.chr7.vcf.gzHD-and-RNA-variants-Chr8.vcfAll HD and RNAseq variants on chromosome 8. Used in the paper for LC and LY GWAS.chr8.vcf.gzHD-and-RNA-variants-Chr9.vcfAll HD and RNAseq variants on chromosome 9. Used in the paper for LC and LY GWAS.chr9.vcf.gzHD-and-RNA-variants-Chr10.vcfAll HD and RNAseq variants on chromosome 10. Used in the paper for LC and LY GWAS.chr10.vcf.gzHD-and-RNA-variants-Chr11.vcfAll HD and RNAseq variants on chromosome 11. Used in the paper for LC and LY GWAS.chr11.vcf.gzHD-and-RNA-variants-Chr12.vcfAll HD and RNAseq variants on chromosome 12. Used in the paper for LC and LY GWAS.chr12.vcf.gzHD-and-RNA-variants-Chr13.vcfAll HD and RNAseq variants on chromosome 13. Used in the paper for LC and LY GWAS.chr13.vcf.gzHD-and-RNA-variants-Chr14.vcfAll HD and RNAseq variants on chromosome 14. Used in the paper for LC and LY GWAS.chr14.vcf.gzHD-and-RNA-variants-Chr15.vcfAll HD and RNAseq variants on chromosome 15. Used in the paper for LC and LY GWAS.chr15.vcf.gzHD-and-RNA-variants-Chr16.vcfAll HD and RNAseq variants on chromosome 16. Used in the paper for LC and LY GWAS.chr16.vcf.gzHD-and-RNA-variants-Chr17.vcfAll HD and RNAseq variants on chromosome 17. Used in the paper for LC and LY GWAS.chr17.vcf.gzHD-and-RNA-variants-Chr18.vcfAll HD and RNAseq variants on chromosome 18. Used in the paper for LC and LY GWAS.chr18.vcf.gzHD-and-RNA-variants-Chr19.vcfAll HD and RNAseq variants on chromosome 19. Used in the paper for LC and LY GWAS.chr19.vcf.gzHD-and-RNA-variants-Chr20.vcfAll HD and RNAseq variants on chromosome 20. Used in the paper for LC and LY GWAS.chr20.vcf.gzHD-and-RNA-variants-Chr21.vcfAll HD and RNAseq variants on chromosome 21. Used in the paper for LC and LY GWAS.chr21.vcf.gzHD-and-RNA-variants-Chr22.vcfAll HD and RNAseq variants on chromosome 22. Used in the paper for LC and LY GWAS.chr22.vcf.gzHD-and-RNA-variants-Chr23.vcfAll HD and RNAseq variants on chromosome 23. Used in the paper for LC and LY GWAS.chr23.vcf.gzHD-and-RNA-variants-Chr24.vcfAll HD and RNAseq variants on chromosome 24. Used in the paper for LC and LY GWAS.chr24.vcf.gzHD-and-RNA-variants-Chr25.vcfAll HD and RNAseq variants on chromosome 25. Used in the paper for LC and LY GWAS.chr25.vcf.gzHD-and-RNA-variants-Chr26.vcfAll HD and RNAseq variants on chromosome 26. Used in the paper for LC and LY GWAS.chr26.vcf.gzHD-and-RNA-variants-Chr27.vcfAll HD and RNAseq variants on chromosome 27. Used in the paper for LC and LY GWAS.chr27.vcf.gzHD-and-RNA-variants-Chr28.vcfAll HD and RNAseq variants on chromosome 28. Used in the paper for LC and LY GWAS.chr28.vcf.gzHD-and-RNA-variants-Chr29.vcfAll HD and RNAseq variants on chromosome 29. Used in the paper for LC and LY GWAS.chr29.vcf.gzvalidation-genotypes-lc.vcfGenotypes of the 22 tag SNPs for the LC phenotype QLT peaks in the 18k validation animals.validation-genotypes-ly.vcfGenotypes of the 5 tag SNPs for the LY phenotype QLT peaks in the 18k validation animals.validation_results_LCThe association statistics for the 22 LC QTL peaks in the 18k animal validation set.lcts_pct_htdat_adj_cgrp_brd.validation.txtvalidation_results_LYThe association statistics for the 5 LY QTL peaks in the 18k animal validation set.lcts_htdat_adj_cgrp_brd.validation.txtREADME fileA description of what all the other files contain.