{"doi":"10.1172/jci135500","title":"Human CRY1 variants associate with attention deficit/hyperactivity disorder","abstract":"Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as \"circiatric\" disorders.","journal":"Journal of Clinical Investigation","year":2020,"id":67352,"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":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9419,"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":356656,"name":"Meltem Ece Kars","orcid":"0000-0001-5922-5608","position":1,"is_corresponding":false},{"id":356657,"name":"Şeref Gül","orcid":"0000-0002-5613-1339","position":2,"is_corresponding":false},{"id":36520,"name":"Kaya Bilgüvar","orcid":"0000-0002-7313-7652","position":3,"is_corresponding":false},{"id":11156,"name":"Yiming Wu","orcid":"0000-0001-5083-8950","position":4,"is_corresponding":false},{"id":356658,"name":"Ayşe Özhan","orcid":"0000-0003-0282-0777","position":5,"is_corresponding":false},{"id":356659,"name":"Cihan Aydın","orcid":"0000-0003-0560-1895","position":6,"is_corresponding":false},{"id":301277,"name":"A. Nazlı Başak","orcid":"0000-0001-6977-2517","position":7,"is_corresponding":false},{"id":357662,"name":"Maria Allegra Trusso","orcid":null,"position":8,"is_corresponding":false},{"id":357663,"name":"Arianna Goracci","orcid":null,"position":9,"is_corresponding":false},{"id":104420,"name":"Chiara Fallerini","orcid":"0000-0002-7386-3224","position":10,"is_corresponding":false},{"id":354090,"name":"Alessandra Renieri","orcid":"0000-0002-0846-9220","position":11,"is_corresponding":false},{"id":57373,"name":"Jean-Laurent Casanova","orcid":"0000-0002-7782-4169","position":12,"is_corresponding":false},{"id":289528,"name":"Yuval Itan","orcid":"0000-0003-4966-3238","position":13,"is_corresponding":false},{"id":356660,"name":"Cem Atbaşoğlu","orcid":"0000-0002-8211-6095","position":14,"is_corresponding":false},{"id":356661,"name":"Meram Can Saka","orcid":"0000-0002-4647-1807","position":15,"is_corresponding":false},{"id":356662,"name":"İbrahim Halil Kavaklı","orcid":"0000-0001-6624-3505","position":16,"is_corresponding":false},{"id":104513,"name":"Tayfun Özçelık","orcid":"0000-0001-5937-1082","position":17,"is_corresponding":false},{"id":356655,"name":"Onur Emre Onat","orcid":"0000-0002-7105-1572","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T21:15:12.020735Z","pmid":"32538895","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":[]}