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While several genetic variants have been associated with specific coat intensity phenotypes in certain dog breeds, they do not explain the majority of phenotypic variation across breeds. In order to gain further insight into the extent of multigenicity and epistatic interactions underlying coat pheomelanin intensity in dogs, we leveraged a large dataset obtained via a direct-to-consumer canine genetic testing service. This consisted of genome-wide single nucleotide polymorphism (SNP) genotype data and owner-provided photos for 3,057 pheomelanic mixed breed and purebred dogs from 63 breeds and varieties spanning the full range of canine coat pheomelanin intensity. We first performed a genome-wide association study (GWAS) on 2,149 of these dogs to search for additional genetic variants that underlie intensity variation. GWAS identified five loci significantly associated with intensity, of which two (CFA15 29.8 Mb and CFA20 55.8 Mb) replicate previous findings and three (CFA2 74.7 Mb, CFA18 12.9 Mb, CFA21 10.9 Mb) have not previously been reported. In order to assess the combined predictive power of these loci across dog breeds, we used our GWAS data set to fit a linear model, which explained over 70% of variation in coat pheomelanin intensity in an independent validation dataset of 908 dogs. These results introduce three novel pheomelanin intensity loci, and further demonstrate the multigenic nature of coat pheomelanin intensity determination in domestic dogs.<\/jats:p>","DOI":"10.1371\/journal.pone.0250579","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T18:41:58Z","timestamp":1622140918000},"page":"e0250579","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Five genetic variants explain over 70% of hair coat pheomelanin intensity variation in purebred and mixed breed domestic dogs"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7791-9267","authenticated-orcid":true,"given":"Andrea J.","family":"Slavney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9204-6852","authenticated-orcid":true,"given":"Takeshi","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0092-8506","authenticated-orcid":true,"given":"Meghan K.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Sams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Boyko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"issue":"1","key":"pone.0250579.ref001","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1038\/ncomms2814","article-title":"The genomics of selection in dogs and the parallel evolution between dogs and humans","volume":"4","author":"G Wang","year":"2013","journal-title":"Nat Commun"},{"issue":"1912","key":"pone.0250579.ref002","first-page":"20190716","article-title":"Highly heritable and functionally relevant breed differences in dog behaviour","volume":"286","author":"EL MacLean","year":"2019","journal-title":"Proc Biol Sci"},{"key":"pone.0250579.ref003","volume-title":"On agriculture: in three volumes. 2: Res rustica V\u2014IX. 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