# Integrating reaction norm models and genome-wide association analyses to reveal the genetic architecture and environmental sensitivity of sexual precocity in Nellore cattle

**Authors:** Eduarda da Silva Oliveira, Hinayah Rojas de Oliveira, Lucio Flavio Macedo Mota, Henrique Alberto Mulim, Milena Aparecida Ferreira Campos, João Barbosa da Silva Neto, Fernando Baldi

PMC · DOI: 10.1186/s12864-026-12547-8 · 2026-01-21

## TL;DR

This study explores how genetics and environment interact to influence early sexual maturity in Nellore cattle, revealing distinct genetic patterns for different traits.

## Contribution

The integration of reaction norm models with GWAS provides new insights into the genetic architecture and environmental sensitivity of sexual precocity traits in cattle.

## Key findings

- Distinct genetic architectures were found for heifer early calving probability, scrotal circumference, and age at puberty.
- Genes like GRB14 and SLC9A8 were linked to both baseline fertility and environmental sensitivity in scrotal circumference.
- Candidate genes for age at puberty were associated with DNA repair and immune regulation pathways.

## Abstract

Reproductive efficiency is an important component of profitability and sustainability in beef cattle production, particularly in tropical environments where animals are routinely exposed to environmental stressors. This study aimed to identify environmentally sensitive SNPs associated with sexual precocity traits in Nellore cattle and characterize candidate genes and biological pathways regulating sexual precocity under variable environmental conditions. For this purpose, three sexual precocity indicators were analyzed; one in heifers (heifer early calving probability at 30 months, HC30), and two in young males (scrotal circumference at 365 days, SC365; age at puberty, APM). Reaction norm models were integrated with genome-wide association studies (GWASs) to identify genomic regions associated with both genetic potential (intercept) and environmental sensitivity (slope).

A total of 46 significant SNPs were identified across the three traits, with SC365 showing the highest genetic complexity (36 SNPs), followed by HC30 (7 SNPs), and APM (3 SNPs). The analyses revealed distinct genetic architectures among the traits. For HC30, candidate genes showed clear functional partitioning between those associated with baseline fertility (e.g., ERBB4, SNAI2) and those associated with environmental sensitivity (e.g., TRIB1, NSMCE2), with no overlap between intercept and slope components. In contrast, SC365 exhibited substantial genetic overlap, with five genes (i.e., GRB14, SLC9A8, SPATA2, MGRN1, SEPTIN12) significantly associated with both intercept and slope, indicating a robust trait with shared genetic control of baseline potential and environmental responsiveness. For APM, genetic associations were predominantly related to baseline potential, with genes involved in DNA repair (CHEK2), endoplasmic reticulum stress response (XBP1), and immune regulation (TNIP3). Functional enrichment analyses revealed trait-specific biological pathways, whereas QTL enrichment demonstrated biologically coherent overlaps with reproductive and metabolic traits.

These findings demonstrate that sexual precocity traits exhibit distinct genetic architectures reflecting their underlying biological mechanisms and environmental responsiveness, providing valuable insights for developing climate-resilient breeding strategies in tropical beef cattle production systems.

The online version contains supplementary material available at 10.1186/s12864-026-12547-8.

## Linked entities

- **Genes:** ERBB4 (erb-b2 receptor tyrosine kinase 4) [NCBI Gene 2066], SNAI2 (snail family transcriptional repressor 2) [NCBI Gene 6591], TRIB1 (tribbles pseudokinase 1) [NCBI Gene 10221], NSMCE2 (NSE2 SUMO ligase component of SMC5/6 complex) [NCBI Gene 286053], GRB14 (growth factor receptor bound protein 14) [NCBI Gene 2888], SLC9A8 (solute carrier family 9 member A8) [NCBI Gene 23315], SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825], MGRN1 (mahogunin ring finger 1) [NCBI Gene 23295], SEPTIN12 (septin 12) [NCBI Gene 124404], CHEK2 (checkpoint kinase 2) [NCBI Gene 11200], XBP1 (X-box binding protein 1) [NCBI Gene 7494], TNIP3 (TNFAIP3 interacting protein 3) [NCBI Gene 79931]

## Full-text entities

- **Diseases:** sexual (MESH:D050035)
- **Species:** Bos taurus (bovine, species) [taxon 9913]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12908385/full.md

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Source: https://tomesphere.com/paper/PMC12908385