{"doi":"10.1101/2020.05.29.20115352","title":"Novel Ultra-Rare Exonic Variants Identified in a Founder Population Implicate Cadherins in Schizophrenia","abstract":"Summary Identification of rare genetic variants associated with schizophrenia has proven challenging due to multiple sources of heterogeneity, which may be reduced in founder populations. We examined ultra-rare exonic variants in 786 patients with schizophrenia and 463 healthy comparison subjects, all drawn from the Ashkenazi Jewish population. Cases had a higher frequency of novel missense or loss of function (MisLoF) variants compared to controls. Characterizing 141 “case-only” genes (in which ≥ 3 cases in our dataset had MisLoF variants with none found in controls), we identified cadherins as a novel gene set associated with schizophrenia, including a recurrent mutation in PCDHA3 . Modeling the effects of purifying selection demonstrated that deleterious ultra-rare variants are greatly over-represented in the Ashkenazi population, resulting in enhanced power for rare variant association. Identification of cell adhesion genes in the cadherin/protocadherin family helps specify the synaptic abnormalities central to the disorder, and suggests novel potential treatment strategies.","journal":"medRxiv","year":2020,"id":122111,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9464,"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":560208,"name":"Jin Yu","orcid":"0000-0002-2990-6602","position":1,"is_corresponding":false},{"id":563835,"name":"Raiyan R. Khan","orcid":null,"position":2,"is_corresponding":false},{"id":289878,"name":"Shai Carmi","orcid":"0000-0002-0188-2610","position":3,"is_corresponding":false},{"id":107833,"name":"Max Lam","orcid":"0000-0002-4256-7844","position":4,"is_corresponding":false},{"id":563836,"name":"Danny Ben‐Avraham","orcid":null,"position":5,"is_corresponding":false},{"id":90076,"name":"Nir Barzilai","orcid":"0000-0002-7787-6268","position":6,"is_corresponding":false},{"id":428933,"name":"Susan Bressman","orcid":"0000-0002-3513-8048","position":7,"is_corresponding":false},{"id":563837,"name":"Ariel Darvasi","orcid":null,"position":8,"is_corresponding":false},{"id":105285,"name":"Judy H. Cho","orcid":"0000-0002-7959-0466","position":9,"is_corresponding":false},{"id":52690,"name":"Lorraine N. Clark","orcid":"0000-0001-5899-4616","position":10,"is_corresponding":false},{"id":51787,"name":"Zeynep H. Gümüş","orcid":"0000-0002-7364-2202","position":11,"is_corresponding":false},{"id":74232,"name":"Vijai Joseph","orcid":"0000-0002-7933-151X","position":12,"is_corresponding":false},{"id":43049,"name":"Robert J. Klein","orcid":"0000-0003-3539-5391","position":13,"is_corresponding":false},{"id":237944,"name":"Steven M. Lipkin","orcid":"0000-0002-0603-9139","position":14,"is_corresponding":false},{"id":108795,"name":"Kenneth Offit","orcid":"0000-0002-2180-2032","position":15,"is_corresponding":false},{"id":536710,"name":"Harry Ostrer","orcid":"0000-0002-2209-5376","position":16,"is_corresponding":false},{"id":342087,"name":"Laurie J. Ozelius","orcid":"0000-0002-7820-1684","position":17,"is_corresponding":false},{"id":432691,"name":"Inga Peter","orcid":"0000-0002-5638-9137","position":18,"is_corresponding":false},{"id":37375,"name":"Anil K. Malhotra","orcid":"0000-0001-9664-4182","position":19,"is_corresponding":false},{"id":1031,"name":"Gil Atzmon","orcid":"0000-0001-6895-3607","position":20,"is_corresponding":false},{"id":305312,"name":"Itsik Pe’er","orcid":"0000-0002-6128-7231","position":21,"is_corresponding":false},{"id":62472,"name":"Todd Lencz","orcid":"0000-0001-8586-338X","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","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":[]}