{"doi":"10.1101/2024.03.13.584852","title":"Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats","abstract":"Abstract Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli (“cues”). Rats exhibited either cue-directed “sign-tracking” behavior or food-cup directed “goal-tracking” behavior. We then used the conditioned reinforcement procedure to determine whether rats would perform a novel operant response for unrewarded presentations of the cue. We found that these measures were moderately heritable (SNP heritability, h 2 = .189-.215). GWAS identified 14 quantitative trait loci (QTLs) for 11 of the 12 traits we examined. Interval sizes of these QTLs varied widely. 7 traits shared a QTL on chromosome 1 that contained a few genes ( e.g. Tenm4 , Mir708 ) that have been associated with substance use disorders and other mental health traits in humans. Other candidate genes ( e.g. Wnt11, Pak1 ) in this region had coding variants and expression-QTLs in mesocorticolimbic regions of the brain. We also conducted a Phenome-Wide Association Study (PheWAS) on other behavioral measures in HS rats and found that regions containing QTLs on chromosome 1 were also associated with nicotine self-administration in a separate cohort of HS rats. These results provide a starting point for the molecular genetic dissection of incentive salience and provide further support for a relationship between attribution of incentive salience and drug abuse-related traits.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486829,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9015,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":813003,"name":"Apurva S. Chitre","orcid":"0000-0003-1709-9214","position":1,"is_corresponding":false},{"id":1330591,"name":"Joel D. Leal‐Gutiérrez","orcid":"0000-0002-2811-5390","position":2,"is_corresponding":false},{"id":1176660,"name":"Jordan A. Tripi","orcid":null,"position":3,"is_corresponding":false},{"id":1330947,"name":"Alesa Hughson","orcid":null,"position":4,"is_corresponding":false},{"id":1330948,"name":"Aidan P. Horvath","orcid":null,"position":5,"is_corresponding":false},{"id":989330,"name":"Alexander Lamparelli","orcid":"0000-0003-1908-9562","position":6,"is_corresponding":false},{"id":1013781,"name":"Anthony M. George","orcid":"0000-0001-5680-8664","position":7,"is_corresponding":false},{"id":328284,"name":"Connor D. Martin","orcid":"0000-0002-6989-5653","position":8,"is_corresponding":false},{"id":275081,"name":"Celine L. St. Pierre","orcid":"0000-0001-5465-6601","position":9,"is_corresponding":false},{"id":737423,"name":"Thiago Missfeldt Sanches","orcid":"0000-0001-6962-9569","position":10,"is_corresponding":false},{"id":1074016,"name":"Hannah Bimschleger","orcid":"0000-0001-6578-7201","position":11,"is_corresponding":false},{"id":104274,"name":"Jianjun Gao","orcid":"0000-0001-6138-4472","position":12,"is_corresponding":false},{"id":601076,"name":"Riyan Cheng","orcid":"0000-0002-8670-795X","position":13,"is_corresponding":false},{"id":1177104,"name":"Khai‐Minh Nguyen","orcid":"0000-0003-3939-7773","position":14,"is_corresponding":false},{"id":977854,"name":"Katie L. Holl","orcid":null,"position":15,"is_corresponding":false},{"id":829431,"name":"Oksana Polesskaya","orcid":"0000-0003-3024-114X","position":16,"is_corresponding":false},{"id":328286,"name":"Keita Ishiwari","orcid":"0000-0002-6190-2249","position":17,"is_corresponding":false},{"id":12579,"name":"Hao Chen","orcid":"0009-0001-6480-7976","position":18,"is_corresponding":false},{"id":551740,"name":"Leah C. Solberg Woods","orcid":"0000-0002-7943-798X","position":19,"is_corresponding":false},{"id":230002,"name":"Abraham A. Palmer","orcid":"0000-0003-3634-0747","position":20,"is_corresponding":false},{"id":708477,"name":"Terry E. Robinson","orcid":"0000-0002-4555-3923","position":21,"is_corresponding":false},{"id":274084,"name":"Shelly B. Flagel","orcid":"0000-0002-7309-9908","position":22,"is_corresponding":false},{"id":451619,"name":"Paul Meyer","orcid":"0000-0001-5665-2292","position":23,"is_corresponding":false},{"id":590310,"name":"Christopher P. King","orcid":"0000-0002-6641-237X","position":0,"is_corresponding":true}],"reference_count":117,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38559127","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}