Nana K. Amissah¹, Christopher P. King¹, Sydney David¹, Destiny Brakey², Luke T Hannan¹, Oksana Polesskaya³, Quinn Carroll², Thiago Missfeldt Sanches³, K. Linnea Volcko²; Apurva Chitre³; Denghui Chen³, Maggie Postolache², Hannah Bimschleger³, Jianjun Gao³, Khai -Ming Nguyen³, Beverly Peng³, Riyan Cheng³, Leah C. Solberg Woods⁴, Abraham A. Palmer^{3, 5}, Derek Daniels^1,2, Paul J. Meyer¹

Maintaining fluid homeostasis is critical for life. Although there are individual variations in the behavioral regulation of fluid homeostasis in rats, the source of these variations is poorly understood. To address this, we conducted a genome-wide association study (GWAS) in 826 male and female heterogenous stock (HS) rats examining multiple phenotypes related to 24-hour food and water intake. Rats were housed in hanging wire cages for 24 hours. Total food intake over the 24-hour test was measured, and drinking was measured via a contact lickometer with millisecond resolution and were subjected to GWAS analyses. Total water intake had moderate genetic correlation with total food intake (r_g = .533), and licks (r_g = .565). There was moderate heritability for traits such as mean licks per burst (h² = .261), total water intake (h² = .224), and burst number (h² = .241). Eight unique loci on chromosomes 1, 2, 7, 12, 14 and 20 were associated with several measures of food and water intake. The locus on chromosome 1 was linked with burst number and mean licks per burst. This locus contained the candidate gene Stx11 which mediates lipid metabolism (Zhang et al., 2022). The locus on chromosome 2 was associated with water intake, and contained the candidate gene Syt6, which is involved in synaptic modulation thorough the brain derived neurotrophic factor (Wong et al., 2015). Food intake linked to a locus on chromosome 14, and contained Paqr3 a gene that regulates glucose and lipid metabolism disorders caused by insulin resistance. These candidate genes were identified by examining eQTL and coding variants. These results demonstrate that the individual differences in food and fluid intake have genetic components. Further studies will examine causal links between the identified candidate genes and ingestive behaviors by directly manipulating these genes using CRISPR-mediated approaches.

¹ Department of Psychology, University at Buffalo, Buffalo, USA.

² Department of Biological Sciences, University at Buffalo, Buffalo, USA.

³ Department of Psychiatry, University of California San Diego, La Jolla, USA.

⁴ Department of Internal Medicine, Molecular Medicine, Center on Diabetes, Obesity and Metabolism, Wake Forest School of Medicine, Winston-Salem, USA.

⁵ Institute for Genomic Medicine, University of California San Diego, La Jolla, USA.

Supported by P50DA037844, U01DA060669, P30DA060810, and R01DK133818