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. 2025 Jun 26;16(7):741.
doi: 10.3390/genes16070741.

Genomic Regions Associated with Respiratory Disease in Holstein Calves in the Southern United States

Allison L Herrick  1 , Jennifer N Kiser  1   2 , Stephen N White  3   4 , Holly L Neibergs  1
Affiliations

Genomic Regions Associated with Respiratory Disease in Holstein Calves in the Southern United States

Allison L Herrick et al. Genes (Basel). .

Abstract

Background/objectives: Bovine respiratory disease (BRD) is a common disease impacting cattle throughout the US. BRD is a multifactorial disease as disease risk varies with the genetic profile of the host, environmental conditions, and pathogen exposure. Selection for enhanced BRD resistant cattle can aid in reducing BRD. The objectives of this study were to identify loci, gene sets, and genes associated and enriched for BRD in pre- and post-weaned Holstein cattle.

Methods: Cases consisted of 2147 and 5607 calves treated for BRD as pre-weaned (0-60 days old) and post-weaned (61-420 days old) calves, respectively. Controls consisted of calves untreated for BRD that remained in the herd for 61 (n = 14,219) days for pre-weaned or 421 (n = 12,242) days for post-weaned calves. A genome-wide association analysis (GWAA) identified loci and positional candidate genes associated with BRD (uncorrected P < 1 × 10-5) for additive, dominant, and recessive inheritance models. A gene set enrichment analysis (GSEA-SNP) identified gene sets and leading-edge genes enriched (NES ≥ 3) for BRD.

Results: In pre-weaned calves, 62 loci and 123 positional candidate genes were associated (P < 1 × 10-5) in addition to the 12 gene sets and 126 leading-edge genes enriched (NES ≥ 3) for BRD. In post-weaned calves, 181 loci and 185 positional candidate genes were associated (P < 1 × 10-5), and 63 gene sets and 849 leading-edge genes were enriched (NES ≥ 3) for BRD.

Conclusions: These results provide further insight and validation of genomic regions that enhance selection for BRD resistance and for healthier cattle.

Keywords: bovine respiratory disease; cattle; gene set enrichment analysis; genome wide association analysis.

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Conflict of interest statement

The authors declare no conflicts of interest, and the funders for this project had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The results for the genome-wide association analysis for bovine respiratory disease are shown for the pre-weaned Holstein heifer calves for the additive inheritance model in (panel A), the dominant inheritance model in (panel B), and the recessive inheritance model in (panel C). Each Manhattan plot has the chromosomes on the x axis and the −log10 p-value on the y axis. The significance thresholds for an association with BRD are represented by the lower line (moderate association with an uncorrected P < 1 × 10−5) and the uppermost line (strong association with an uncorrected P < 5 × 10−7).
Figure 2
Figure 2
The results for the genome-wide association analysis for bovine respiratory disease are shown for the post-weaned Holstein heifer calves for the additive inheritance model in (panel A), the dominant inheritance model in (panel B), and the recessive inheritance model in (panel C). Each Manhattan plot has the Bos taurus chromosomes (BTA) on the x axis and the −log10 p-value on the y axis. The significance thresholds for an association with BRD are represented by the lower line (moderate association with an uncorrected P < 1 × 10−5) and the uppermost line (strong association with an uncorrected P < 5 × 10−7).
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