{"doi":"10.17615/66m2-7983","title":"Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2)","abstract":"Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG.","journal":"UNC Libraries","year":2020,"id":139923,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":5340,"name":"Nicholas G. Martin","orcid":"0000-0003-4069-8020","position":1,"is_corresponding":false},{"id":5254,"name":"Sarah E. Medland","orcid":"0000-0003-1382-380X","position":2,"is_corresponding":false},{"id":603470,"name":"Patrick Mullin","orcid":"0000-0001-9688-9841","position":3,"is_corresponding":false},{"id":5374,"name":"Lucía Colodro‐Conde","orcid":"0000-0002-9004-364X","position":4,"is_corresponding":false},{"id":104444,"name":"Per Magnus","orcid":"0000-0002-6427-4735","position":5,"is_corresponding":false},{"id":49873,"name":"Päivi Pajukanta","orcid":"0000-0002-6423-8056","position":6,"is_corresponding":false},{"id":604113,"name":"Mitsu Reddy","orcid":null,"position":7,"is_corresponding":false},{"id":282708,"name":"Janet S. Sinsheimer","orcid":"0000-0001-9540-5956","position":8,"is_corresponding":false},{"id":603471,"name":"Ronny Myhre","orcid":"0000-0002-2858-8681","position":9,"is_corresponding":false},{"id":109341,"name":"Margaret J. Wright","orcid":"0000-0001-7133-4970","position":10,"is_corresponding":false},{"id":603472,"name":"Marlena S. Fejzo","orcid":"0000-0001-6800-687X","position":11,"is_corresponding":false},{"id":339701,"name":"Stephanie M. Engel","orcid":"0000-0002-3942-1246","position":12,"is_corresponding":false},{"id":5265,"name":"Dale R. Nyholt","orcid":"0000-0001-7159-3040","position":13,"is_corresponding":false},{"id":603469,"name":"Kimber MacGibbon","orcid":"0000-0002-6534-3114","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:13.583586Z","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":[]}