{"doi":"10.1002/jcv2.12143","title":"Family environment and polygenic risk in the bipolar high‐risk context","abstract":"Background: The interaction of polygenic risk (PRS) and environmental effects on development of bipolar disorder (BD) is understudied, as are high-risk offspring perceptions of their family environment (FE). We tested the association of offspring-perceived FE in interaction with BD-PRS on liability for BD in offspring at high or low familial risk for BD. Methods: = 174), aged 12-21 at recruitment, participated in the US and Australia. Empirically-derived profiles of FE classified offspring by their perceived levels of familial cohesion, flexibility, and conflict. Offspring BD-PRS were derived from Psychiatric Genomics Consortium BD-GWAS. Lifetime DSM-IV bipolar disorders were derived from the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. We used a novel stepwise approach for latent class modeling with predictors and distal outcomes. Results: Fifty-two offspring were diagnosed with BD. For those with well-functioning FE (two-thirds of the sample), higher BD-PRS tracked positively with liability for BD. However, for those with high-conflict FEs, the relationship between BD-PRS and liability to BD was negative, with highest risk for BD observed with lower BD-PRS. In exploratory analyses, European-ancestry offspring with BD had elevated history of suicidal ideation in high-conflict FE compared to well-functioning-FE, and of suicide attempt with low-BD-PRS and high-conflict FE. Conclusions: The data suggest that the relationship of BD-PRS and offspring liability for BD differed between well-functioning versus high-conflict FE, potentially in line with a multifactorial liability threshold model and supporting future study of and interventions improving family dynamics.","journal":"JCPP Advances","year":2023,"id":363346,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7102,"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":235077,"name":"Janice M. Fullerton","orcid":"0000-0003-4014-4490","position":1,"is_corresponding":false},{"id":627465,"name":"Rashelle J. Musci","orcid":"0000-0001-7267-5822","position":2,"is_corresponding":false},{"id":489035,"name":"Peter P. Zandi","orcid":"0000-0001-8423-2623","position":3,"is_corresponding":false},{"id":362434,"name":"Melvin G. McInnis","orcid":"0000-0002-0375-6247","position":4,"is_corresponding":false},{"id":68425,"name":"Philip B. Mitchell","orcid":"0000-0002-7954-5235","position":5,"is_corresponding":false},{"id":446082,"name":"Leslie A. Hulvershorn","orcid":"0000-0001-5827-4889","position":6,"is_corresponding":false},{"id":729505,"name":"Neera Ghaziuddin","orcid":"0000-0002-7381-3948","position":7,"is_corresponding":false},{"id":237645,"name":"Gloria Roberts","orcid":"0000-0002-1966-5120","position":8,"is_corresponding":false},{"id":1057934,"name":"Alessandra G. Ferrera","orcid":null,"position":9,"is_corresponding":false},{"id":40253,"name":"John I. Nürnberger","orcid":"0000-0002-7674-1767","position":10,"is_corresponding":false},{"id":314818,"name":"Holly C. Wilcox","orcid":"0000-0003-2624-0654","position":11,"is_corresponding":false},{"id":242714,"name":"Emma K. Stapp","orcid":"0000-0003-0628-0704","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:14:28.054440Z","pmid":"37378048","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":[]}