{"doi":"10.17615/t6b3-ke37","title":"Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder","abstract":"We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10−8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.","journal":"UNC Libraries","year":2020,"id":117748,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8055,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":549111,"name":"Craddock,","orcid":null,"position":1,"is_corresponding":false},{"id":549112,"name":"Moran,","orcid":null,"position":2,"is_corresponding":false},{"id":543509,"name":"Perlis,","orcid":null,"position":3,"is_corresponding":false},{"id":549113,"name":"Ruderfer,","orcid":null,"position":4,"is_corresponding":false},{"id":549114,"name":"Lichtenstein","orcid":null,"position":5,"is_corresponding":false},{"id":549115,"name":"Jones","orcid":null,"position":6,"is_corresponding":false},{"id":549116,"name":"Chambert,","orcid":null,"position":7,"is_corresponding":false},{"id":549117,"name":"Rakofsky","orcid":null,"position":8,"is_corresponding":false},{"id":549118,"name":"Charney,","orcid":null,"position":9,"is_corresponding":false},{"id":549119,"name":"Stahl,","orcid":null,"position":10,"is_corresponding":false},{"id":549120,"name":"Knowles,","orcid":null,"position":11,"is_corresponding":false},{"id":549121,"name":"Roussos,","orcid":null,"position":12,"is_corresponding":false},{"id":549122,"name":"Fanous","orcid":null,"position":13,"is_corresponding":false},{"id":549123,"name":"Lee,","orcid":null,"position":14,"is_corresponding":false},{"id":549124,"name":"Lehrer","orcid":null,"position":15,"is_corresponding":false},{"id":549125,"name":"Malaspina","orcid":null,"position":16,"is_corresponding":false},{"id":549126,"name":"Fochtmann","orcid":null,"position":17,"is_corresponding":false},{"id":549127,"name":"Sobell","orcid":null,"position":18,"is_corresponding":false},{"id":549128,"name":"Backlund","orcid":null,"position":19,"is_corresponding":false},{"id":549129,"name":"Bromet,","orcid":null,"position":20,"is_corresponding":false},{"id":543538,"name":"Smoller","orcid":null,"position":21,"is_corresponding":false},{"id":549130,"name":"Sklar,","orcid":null,"position":22,"is_corresponding":false},{"id":549131,"name":"Morley,","orcid":null,"position":23,"is_corresponding":false},{"id":549132,"name":"Hultman","orcid":null,"position":24,"is_corresponding":false},{"id":534013,"name":"Buckley,","orcid":null,"position":25,"is_corresponding":false},{"id":549133,"name":"Green,","orcid":null,"position":26,"is_corresponding":false},{"id":549134,"name":"Forty,","orcid":null,"position":27,"is_corresponding":false},{"id":549135,"name":"Nicolini,","orcid":null,"position":28,"is_corresponding":false},{"id":549136,"name":"Belliveau,","orcid":null,"position":29,"is_corresponding":false},{"id":549137,"name":"Bergen,","orcid":null,"position":30,"is_corresponding":false},{"id":549138,"name":"Pato,","orcid":null,"position":31,"is_corresponding":false},{"id":549139,"name":"Marder,","orcid":null,"position":33,"is_corresponding":false},{"id":549140,"name":"Juréus,","orcid":null,"position":34,"is_corresponding":false},{"id":549141,"name":"Jones,","orcid":null,"position":36,"is_corresponding":false},{"id":549142,"name":"Escamilla","orcid":null,"position":37,"is_corresponding":false},{"id":549143,"name":"Medeiros","orcid":null,"position":38,"is_corresponding":false},{"id":549144,"name":"McCarroll","orcid":null,"position":39,"is_corresponding":false},{"id":549145,"name":"Purcell,","orcid":null,"position":42,"is_corresponding":false},{"id":549146,"name":"Perkins,","orcid":null,"position":43,"is_corresponding":false},{"id":549147,"name":"Lehrer,","orcid":null,"position":44,"is_corresponding":false},{"id":549110,"name":"Di Florio,","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:54.951170Z","pmid":null,"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":[]}