{"doi":"10.1002/ajmg.b.32964","title":"Novel genome‐wide associations for effort valuation and psychopathology in children and adults","abstract":"The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder-agnostic framework for analysis of human psychopathology through designated domains and constructs, including the \"Positive Valence Systems\" domain focused on reward-related behavior. This study investigates the reward valuation subconstruct of \"effort\" and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6-12 and their parents (n = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses \"effort\" according to two quantitative measures: hard-task choice and reward sensitivity. Genetic association analyses were undertaken in MAGMA, utilizing EEfRT outcome variables as genome-wide association studies phenotypes to compute SNP and gene-level associations. Genome-wide association analyses found two distinct genetic loci that were significantly associated with measures of reward sensitivity and a separate genetic locus associated with hard task choice. Gene-set enrichment analysis yielded significant associations between \"effort\" and multiple gene sets involved in reward processing-related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish \"effort\" as a relevant construct for understanding reward-related behavior at the genetic level and support the RDoC framework for assessing disorder-agnostic psychopathology.","journal":"American Journal of Medical Genetics Part B Neuropsychiatric Genetics","year":2023,"id":385602,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8605,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":730187,"name":"Tommaso Mazza","orcid":"0000-0003-0434-8533","position":1,"is_corresponding":false},{"id":542544,"name":"Jonathan Hess","orcid":"0000-0001-8406-632X","position":2,"is_corresponding":false},{"id":543197,"name":"Avery B. Albert","orcid":null,"position":3,"is_corresponding":false},{"id":1154023,"name":"Sarah Elfstrom","orcid":null,"position":4,"is_corresponding":false},{"id":542548,"name":"Patricia Forken","orcid":"0000-0002-9931-9753","position":5,"is_corresponding":false},{"id":993192,"name":"Steven D. Blatt","orcid":"0000-0003-0627-4478","position":6,"is_corresponding":false},{"id":289653,"name":"Wanda Fremont","orcid":"0000-0002-0439-6116","position":7,"is_corresponding":false},{"id":109307,"name":"Stephen V. Faraone","orcid":"0000-0002-9217-3982","position":8,"is_corresponding":false},{"id":1060,"name":"Stephen J. Glatt","orcid":"0000-0002-0360-7567","position":9,"is_corresponding":false},{"id":542545,"name":"Nicholas H. Nguyen","orcid":"0000-0002-0744-1920","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:17:52.636565Z","pmid":"37953388","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":[]}