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In the present study, whole genome sequencing (WGS) of 9 CKCS cases (mitral regurgitation (MR) before 4.5\u2009years or congestive heart failure (CHF) at any age due to MMVD) and 10 CKCS controls (no or mild MR after 8\u2009years of age) identified &gt;\u20092000 genetic variants in the MMVD associated cfa13 and cfa14 regions. Ensembl Variant Effect Predictor (VEP) identified a possible functional impact of 18 variants. These were genotyped in 250 CKCS; 117 cases and 133 controls. The most significantly associated variants were a splice\u2010site variant in a long noncoding RNA (lncRNA) on cfa13, a nonsynonymous variant in\n                    <jats:italic>HYAL4<\/jats:italic>\n                    , a 39 base\u2010pair insertion in\n                    <jats:italic>LMOD2<\/jats:italic>\n                    and a synonymous variant in ENSCAFG00000024436 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010values from 2.03E\u201008 to 4.20E\u201006). Concomitant homozygosity for risk alleles in\n                    <jats:italic>LMOD2<\/jats:italic>\n                    and the lncRNA gave an odds\u2010ratio for MMVD of 52.5 compared to homozygosity for the nonrisk alleles (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.00034, 95% CI: 8.8\u20131023.8). Upon validation of our results in an independent cohort, this gene variant combination in CKCS is expected to enable targeted breeding programs to reduce MMVD prevalence in CKCS.\n                  <\/jats:p>","DOI":"10.1002\/age.70200","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:55:54Z","timestamp":1788868554000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Combination of Alleles in\n                    <i>LMOD2<\/i>\n                    and a\n                    <scp>lncRNA<\/scp>\n                    is Strongly Associated With Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0292-3111","authenticated-orcid":false,"given":"Lisbeth H\u00f8ier","family":"Olsen","sequence":"first","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arney Eva","family":"Gunnlaugsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2123-8483","authenticated-orcid":false,"given":"Majbritt Busk","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Jane","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Josefine Ubbe","family":"Reimann","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8188-7765","authenticated-orcid":false,"given":"Foteini","family":"Papadaki","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-0454","authenticated-orcid":false,"given":"Ingrid","family":"Ljungvall","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-023X","authenticated-orcid":false,"given":"Jens","family":"H\u00e4ggstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Swedish University of Agricultural Sciences  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9760-6791","authenticated-orcid":false,"given":"Torben","family":"Martinussen","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Copenhagen  Copenhagen K Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-5134","authenticated-orcid":false,"given":"Henrik Duelund","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torkel","family":"Falk","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merete","family":"Fredholm","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-2763","authenticated-orcid":false,"given":"Peter","family":"Karlskov\u2010Mortensen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences University of Copenhagen  Frederiksberg C 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