Although geese possess an adaptive physiological capacity for lipid storage, few candidate genes contributing to this ability are characterised. By comparing the genomes of individuals with extremely high and low fatty liver weights (FLW), candidate genes were identified, including ARAP2, GABRE, and IL6. Single-nucleotide polymorphisms in or near these genes were significantly (p < 0.05) associated with carcass traits (FLW) and biochemical indexes (very-low-density lipoprotein and N-terminal procollagen III), suggesting contribution to trait variation. A common variant at the 5′-end of LCORL explained ~ 18% and ~ 26% of the phenotypic variance in body weight with/without overfeeding and had significant effects on FLW (p < 0.01). ZFF36L1, ARHGEF1 and IQCJ, involved in bile acid metabolism, blood pressure, and lipid concentration modulation, were also identified. The presence of highly divergent haplotypes within these genes suggested involvement in protection against negative effects from excessive lipids in the liver or circulatory system. Based on this and transcriptomic data, we concluded that geese hepatosteatosis results from severe imbalance between lipid accumulation and secretion, comparable to human non-alcohol fatty liver disease but involving other genes. Our results provided valuable insights into the genesis of geese fatty liver and detected potential target genes for treatment of lipid-related diseases. Migratory birds are physiologically adapted to accumulating large amounts of lipids (more than 50% of their body weight) and efficiently utilising the stored fatty acids to endure flights of many days to arrive at their target habitats 1. The domestic goose was domesticated from the greylag goose (Anser Anser) or swan goose (Anser Cygnoides), both of which are migratory birds, and its retained ability to accumulate lipids has been the foundation for the establishment of the fatty liver (foie gras) industry 2,3. In selected geese, hepatic weight can increase more than eightfold in 2 weeks and account for more than 9% of the body weight 4. Geese are considered an interesting model for understanding the pathogenesis of non-alcohol fatty liver disease (NAFLD) in human owing to multiple shared physiological properties 5. NAFLD is an expanding health threat, with up to 25% global prevalence, and is becoming a heavy economic burden in many countries 6. In the last decade, with the help of next-generation sequencing platforms, large-scale genome-wide association studies (GWAS) have led to the identification of an enormous number of sequence variations related to this chronic liver disease 7-10. To date, more than five genes have been robustly demonstrated to be associated with NAFLD. These include PNPLA3, TM6SF2, GCKR, MBOAT7, and HSD17B13 11. PNPLA3 encodes the patatin-like phospholipase domain-containing 3 protein and has the most robust association with NAFLD: a common missense variant (rs738409, I148M) with NAFLD. This loss-of-function mutation disrupts the PNPLA3 enzyme activity, resulting in impaired mo...