Genome-wide association and genomic prediction for a reproductive index summarizing fertility outcomes in U.S. Holsteins

Subfertility represents one major challenge to enhancing dairy production and efficiency. Herein, we use a reproductive index (RI) expressing the predicted probability of pregnancy following artificial insemination with Illumina 778K genotypes to perform single and multi-locus genome-wide association analyses (GWAA) on 2,448 geographically diverse U.S. Holstein cows and produce genomic heritability estimates. Moreover, we use genomic best linear unbiased prediction (GBLUP) to investigate the potential utility of the RI by performing genomic predictions with cross-validation. Notably, genomic heritability estimates for the U.S. Holstein RI were moderate ( 0.1654± 0.0317 – 0.2550 ± 0.0348), while single and multi-locus GWAA revealed overlapping quantitative trait loci (QTL) on BTA6 and BTA29, including known QTL for daughter pregnancy rate (DPR) and cow conception rate (CCR). Multi-locus GWAA revealed seven additional QTL, including one on BTA7 (60 Mb) which is adjacent to a known heifer ..., Summary data from single-locus and multi-locus genome wide association analyses are summarized in Additional File 1 and Additional File 2, respectively. Summary data from GBLUP-based genomic predictions with k-fold cross-validation are summarized in Additional File 3. Summary statistics for milk yield (up to 90 days of lactation, MAVG90kg) in high-fertility and low-fertility individuals are described in Additional File 4., The files are annotated in detail and self-explanatory when evaluated within the context of the manuscript. See the ReadMe.亚生育力是制约乳品生产效率提升的核心挑战之一。本研究利用可表征人工授精后妊娠预测概率的繁殖指数（reproductive index, RI），结合Illumina 778K基因分型数据，对2448头地理分布广泛的美国荷斯坦奶牛开展单基因座与多基因座全基因组关联分析（genome-wide association analyses, GWAA），并估算基因组遗传力。此外，本研究采用基因组最佳线性无偏预测（genomic best linear unbiased prediction, GBLUP）方法，通过k折交叉验证开展基因组预测，以探究该繁殖指数的应用潜力。值得注意的是，美国荷斯坦奶牛繁殖指数的基因组遗传力估计值处于中等水平（0.1654±0.0317 ~ 0.2550±0.0348）；单基因座与多基因座GWAA均在牛常染色体6号（BTA6）和29号（BTA29）上发现了重叠的数量性状基因座（quantitative trait loci, QTL），其中包含已知的与女儿妊娠率（daughter pregnancy rate, DPR）及母牛受胎率（cow conception rate, CCR）相关的QTL。多基因座GWAA还额外发现了7个QTL，包括位于牛常染色体7号（BTA7）60 Mb处、邻近已知青年母牛相关位点的QTL……单基因座与多基因座全基因组关联分析的汇总数据分别详见附加文件1与附加文件2。基于GBLUP的k折交叉验证基因组预测汇总数据详见附加文件3。高繁殖力与低繁殖力个体的泌乳前90天平均产奶量（MAVG90kg）统计信息详见附加文件4。所有文件均已进行详细注释，结合本论文语境即可自行理解，详见说明文档（ReadMe）。