{"doi":"10.3390/genes13040636","title":"Rare and Common Variants Uncover the Role of the Atria in Coarctation of the Aorta","abstract":"Coarctation of the aorta (CoA) and bicuspid aortic valve (BAV) often cooccur and are genetically linked congenital heart defects (CHD). While CoA is thought to have a hemodynamic origin from ventricular dysfunction, we provide evidence pointing to atrial hemodynamics based on investigating the genetic etiology of CoA. Previous studies have shown a rare MYH6 variant in an Icelandic cohort, and two common deletions in the protocadherin α cluster (PCDHA delCNVs) are significantly associated with CoA and BAV. Here, analysis of a non-Icelandic white CHD cohort (n = 166) recovered rare MYH6 variants in 10.9% of CoA and 32.7% of BAV/CoA patients, yielding odds ratios of 18.6 (p = 2.5 × 10−7) and 20.5 (p = 7.4 × 10−5) for the respective association of MYH6 variants with CoA and BAV/CoA. In combination with the PCHDA delCNVs, they accounted for a third of CoA cases. Gene expression datasets for the human and mouse embryonic heart showed that both genes are predominantly expressed in the atria, not the ventricle. Moreover, cis-eQTLs analysis showed the PCHDA delCNV is associated with reduced atrial expression of PCHDA10, a gene in the delCNV interval. Together, these findings showed that PCDHA/MYH6 variants account for a substantial fraction of CoA cases. An atrial rather than ventricular hemodynamic model for CoA is indicated, consistent with the known early atrial functional dominance of the human embryonic heart.","journal":"Genes","year":2022,"id":278565,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":733840,"name":"Kylia Williams","orcid":"0000-0003-1163-4546","position":1,"is_corresponding":false},{"id":328703,"name":"Cullen B. Young","orcid":"0000-0002-6283-0531","position":2,"is_corresponding":false},{"id":328706,"name":"Jiuann‐Huey Lin","orcid":"0000-0003-3029-6079","position":3,"is_corresponding":false},{"id":317435,"name":"Polakit Teekakirikul","orcid":"0000-0003-2407-7355","position":4,"is_corresponding":false},{"id":314377,"name":"Cecilia Lo","orcid":"0000-0003-4314-3434","position":5,"is_corresponding":false},{"id":733839,"name":"Wenjuan Zhu","orcid":"0000-0003-2724-4825","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-19T00:28:47.357993Z","pmid":"35456442","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":[]}