The leopard coral grouper (Plectropomus leopardus) belongs to the family Epinephelinae, and genus Plectropomus. Vibrio harveyi is the main pathogen that causes "rot disease" in leopard coral grouper, which is a major threat to the sustainable development of its aquaculture industry. The disease is highly prevalent from June to August and severely affects aquaculture. Therefore, developing disease-resistant strains is a necessity. However, currently, artificial breeding techniques for leopard coral groupers cannot establish a family lineage through one-on-one artificial insemination, making traditional breeding methods that depend on a clear pedigree difficult. Considering the successful breeding of disease-resistant fish species with or without a pedigree, genome selection breeding technology are vital for cultivating disease-resistant leopard coral groupers.In genetic selection, the genetic parameters of target traits are important reference factors for specifying breeding programs. To evaluate the genetic parameters of leopard coral grouper resistance to V. harveyi, we constructed a genome-relatedness matrix based on high-density single-nucleotide polymorphisms using four models (binary linear model [BLM], binary threshold model [BTM], longitudinal linear model [LLM], and linear threshold model [LTM]) to fit two disease-resistant phenotypes (test-day trait, TDS; Bivariate survival trait, TS), and used restricted maximum likelihood [REML] to estimate variance components. Our findings illustrated that the genetic heritability of leopard coral grouper resistance to V. harveyi ranged from 0.182 to 0.486, which belongs to the medium-to-high genetic heritability range. The additive genetic variance ranged from 0.071 to 0.262. The genetic heritability estimated by the linear model was 0.382 and 0.476, whereas that estimated by the threshold model was 0.182 and 0.207, respectively. These results suggest that leopard coral groupers resistance to V. harveyi can be improved through genetic breeding.Herein, the linear models (BLM and LLM) obtained higher genetic heritability estimates and more accurate genomic estimated breeding value (GEBV) predictions than the threshold models (BTM and LTM). However, despite the model used, the correlation coefficient between the GEBV rankings under the same phenotype definition > 0.9, indicating that their impact on the GEBV ranking was not significant. Compared to the cross-sectional models (BLM and BTM), numerous leopard coral grouper GEBVs were rearranged in the LLM results. There was a strong correlation between the LTM and phenotype (TS), indicating that LLM has an excellent prediction effect. Therefore, when breeding leopard coral groupers for V. harveyi-resistant traits, a LLM should be considered.The study observed that using longitudinal models (LLM and LTM) to estimate genetic heritability produced higher results than the cross-sectional models (BLM and BTM), which may be due to the death time explaining different components of fish disease resistance. In longitudinal models, the genetic component influenced by the time of death is effectively harnessed. However, in cross-sectional models, this effect is inadvertently subsumed within the residuals. Consistent with the genetic heritability findings, the longitudinal models produced more precise GEBVs compared to cross-sectional models. Our results suggest that TDS might offer a more accurate measure for assessing the resistance of leopard coral groupers to V. harveyi than the TS.Compared with the threshold models, linear models performed better in GEBV prediction, and higher genetic heritability estimates were obtained. Although, most previous studies on disease resistance traits have reported inconsistent genetic heritability estimates between threshold and linear models, some studies support these conclusions. This result may be due to differences in information processing between the different models, which leads to different results. In this study, the additive genetic variance obtained using threshold models (BTM and LTM) was 0.222–0.262, and additive genetic variance obtained using linear models (LLM and BLM) was 0.071–0.086. It is expected that the additive genetic variance obtained using threshold models was higher than that obtained using linear models. Furthermore, the residual variance resulting from fitting linear models was notably low. We posit that when threshold traits are erroneously treated as normally distributed data and linear models are employed for analysis, the residual variance may be underestimated. This underestimation is likely due to the model's underfitting, which consequently leads to an inflated heritability estimate for the linear model.This study aimed to estimate the genetic parameters of leopard coral grouper resistance to V. harveyi using infection test data of leopard coral groupers injected with V. harveyi and to construct an individual genotype relationship matrix based on single-nucleotide polymorphisms. The genetic heritability of leopard coral grouper resistance to V. harveyi was estimated to be between 0.182 and 0.486 by comparing different models and phenotype definitions. The linear (0.382 and 0.476) and threshold models (0.182 and 0.207) were used to estimate genetic heritability. The estimated genetic heritability was within the medium genetic heritability range. Our findings were used to improve the target traits of leopard coral groupers, specifically their resistance to V. harveyi. This study supplements the genetic parameter estimation of leopard coral grouper resistance to V. harveyi and provides a reference for selecting V. harveyi-resistant leopard coral groupers for breeding.