# Using single-step genome-wide association analyses to compare predicted negative energy balance and a novel energy deficiency score in early-lactation Holstein cows

## TL;DR

This study compares two genetic indicators of energy imbalance in dairy cows to better understand their genetic and biological differences.

## Contribution

The study introduces a novel energy deficiency score and compares its genetic architecture with a traditional NEB proxy using advanced genomic methods.

## Key findings

- LPNEB and LEDS share some genomic regions but also have distinct genetic architectures.
- Candidate genes and biological pathways related to energy metabolism and neuronal signaling were identified.
- The study highlights genetic links between energy balance and traits like fertility and somatic cell score.

## Abstract

Summary: This study compared the genetic architectures of 2 mid-infrared (MIR)-predicted proxies of negative energy balance (NEB) in early-lactation Holstein cows: the logit-transformed predicted NEB (LPNEB) and the logittransformed energy deficiency score (LEDS). Using single-step genome-wide association study (ssGWAS) and functional enrichment analysis, the results revealed both overlapping and distinct genomic regions, biological pathways, and candidate genes for the 2 traits. These findings improve our understanding of the genetic background of LPNEB and LEDS, thereby providing new insights into the mechanisms underlying energy balance in dairy cattle. QTL = quantitative trait loci; SCS = somatic cell score.

Summary: This study compared the genetic architectures of 2 mid-infrared (MIR)-predicted proxies of negative energy balance (NEB) in early-lactation Holstein cows: the logit-transformed predicted NEB (LPNEB) and the logittransformed energy deficiency score (LEDS). Using single-step genome-wide association study (ssGWAS) and functional enrichment analysis, the results revealed both overlapping and distinct genomic regions, biological pathways, and candidate genes for the 2 traits. These findings improve our understanding of the genetic background of LPNEB and LEDS, thereby providing new insights into the mechanisms underlying energy balance in dairy cattle. QTL = quantitative trait loci; SCS = somatic cell score.

•Two MIR-predicted NEB proxies (LPNEB and LEDS) were compared in Holstein cows.•Both LPNEB and LEDS exhibit polygenic architectures.•This study provides new insights into the mechanisms underlying energy balance.

Two MIR-predicted NEB proxies (LPNEB and LEDS) were compared in Holstein cows.

Both LPNEB and LEDS exhibit polygenic architectures.

This study provides new insights into the mechanisms underlying energy balance.

This study aimed to compare the genetic architectures of logit-transformed predicted negative energy balance (LPNEB) and a novel logit-transformed energy deficiency score (LEDS) as 2 mid-infrared–derived proxies of negative energy balance in early-lactation dairy cows. A total of 30,634 records from 25,287 first-parity Holstein cows across 508 herds distributed in Walloon region of Belgium were analyzed. Genotypic data of 566,170 SNPs were available for 3,757 animals. Single-step GWAS, combined with a 50-SNP sliding window approach, was employed to explore the genetic architectures of LPNEB and LEDS. The top 10 genomic regions for LPNEB and LEDS were identified across multiple chromosomes, with 3 shared regions (BTA 1, 5, and 16). Despite these overlaps, each trait exhibited unique loci, supporting distinct genetic architectures. Positional candidate gene analyses identified 17 genes for LPNEB and 10 for LEDS, with 6 being in common. Gene Ontology enrichment analyses were then performed to explore their biological functions, although LPNEB was primarily associated with energy metabolism regulation and metabolic adaptation, whereas LEDS integrated neuronal signaling into energy homeostasis. The QTL enrichment highlighted significant associations with fertility and SCS, reinforcing a genetic basis for energy balance. These findings improve our understanding of the genetic background of LPNEB and LEDS, thereby providing new insights into the mechanisms underlying energy balance in dairy cattle.