Genetic Variants Associated with Milk Yield and Composition in Goats: Systematic Review and Genomic Annotation of Reliable Markers

Goat milk demand is rising, but genetic improvement lags behind cattle owing to limited genomic resources and validated markers. This systematic review evaluated variants associated with goat milk yield and composition and standardized their annotation. Following PRISMA 2020, PubMed and Web of Science were searched (to July 2025); 69 studies (37,308 animals, 43 breeds) from 2301 records were included. A total of 318 significant variants (SNPs, indels, CNVs) were re-annotated onto the ARS1.2 reference genome. The chromosome 6 casein cluster (CSN1S1, CSN1S2, CSN2, CSN3) was the most studied region, whereas GWAS identified a multi-trait QTL on chromosome 19 (24.5–29 Mb) for milk yield, fat, and protein. Only five genes (CSN1S1, CSN1S2, CSN3, DGAT1, ITGB4) overlapped between candidate gene and GWAS approaches. CSN1S2 (chr6:86088687 G/C), DGAT1 (chr14:81337119 G>T, chr14:81338102 C>T, chr14:81334974), PRLR (chr20:39081129 C>T), and LTF (chr22:52981144 G/A) variants showed the most consistent associations and are considered most reliable; most others, reported in single studies, remain unvalidated. A total of 39.34% (24/61) of candidate gene studies could not be re-annotated owing to incomplete sequences or outdated or heterologous reference genomes. Reporting only significant loci may inflate reliability (winner’s curse); English-only, two-database searches may add bias. This research offers a standardized resource and urges better genomic reporting.