{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:31:52Z","timestamp":1767918712402,"version":"3.49.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Calcium ions (Ca<jats:sup>2+<\/jats:sup>) play an essential role in excitation\u2013contraction coupling in the heart. The association between cardiovascular diseases (CVDs) and genetic polymorphisms in key regulators of Ca<jats:sup>2+<\/jats:sup> homeostasis is well established but still inadequately understood.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The associations of 11,274 genetic variants located in nine calcium signaling-related genes with 118 diseases of the circulatory system were explored using a large sample from the United Kingdom Biobank (<jats:italic>N<\/jats:italic> = 308,366). The clinical outcomes in electronic health records were mapped to the phecode system. Survival analyses were employed to study the role of variants in CVDs incidence and mortality. Phenome-wide association studies (PheWAS) were performed to investigate the effect of variants on cardiovascular risk factors.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The reported association between rs1801253 in \u03b21-adrenergic receptor (ADRB1) and hypertension was successfully replicated, and we additionally found the blood pressure-lowering G allele of this variant was associated with a delayed onset of hypertension and a decreased level of apolipoprotein A. The association of rs4484922 in calsequestrin 2 (CASQ2) with atrial fibrillation\/flutter was identified, and this variant also displayed nominal evidence of association with QRS duration and carotid intima-medial thickness. Moreover, our results indicated suggestive associations of rs79613429 in ryanodine receptor 2 (RYR2) with precordial pain.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Multiple novel associations established in our study highlight genetic testing as a useful method for CVDs diagnosis and prevention.<\/jats:p>","DOI":"10.3389\/fcell.2021.642141","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T11:33:17Z","timestamp":1638358397000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Association Study of Genetic Variants in Calcium Signaling-Related Genes With Cardiovascular Diseases"],"prefix":"10.3389","volume":"9","author":[{"given":"Sen","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaoqi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1126\/science.1156409","article-title":"Genetic mapping in human disease.","volume":"322","author":"Altshuler","year":"2008","journal-title":"Science"},{"key":"B2","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/ng.3014","article-title":"Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.","volume":"46","author":"Arking","year":"2014","journal-title":"Nat. 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