{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:58:44Z","timestamp":1785927524684,"version":"3.56.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Idiopathic ventricular tachycardia (VT) occurs in structurally normal hearts and accounts for a significant number of all types of VT. The genome-wide association study is the most effective strategy for identifying novel genetic variants for common diseases. However, no genome-wide association study has been reported for idiopathic VT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We conducted the first genome-wide association study for idiopathic VT in the Chinese Han population using a discovery population with 246 cases and 648 controls and a replication population with 222 cases and &gt;4072 controls. Candidate VT genes were functionally characterized in zebrafish. Real-time RT-PCR analysis was used to determine the effects of candidate genes on expression of ion channels and regulators. Patch-clamping was used to record L-type calcium current from neonatal rat cardiomyocytes with overexpression of candidate genes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We identified 4 significant loci represented by rs78960694 (minor allele frequency [MAF]=5.02% in cases and 1.84% in controls;\n              <jats:italic>P<\/jats:italic>\n              =4.30\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              12, odds ratio [OR]=3.91) and rs2229095 (MAF=3.25% in cases and 1.63% in controls;\n              <jats:italic>P<\/jats:italic>\n              =1.02\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              7, OR=3.44) near and in\n              <jats:italic>CCR7<\/jats:italic>\n              , respectively, rs68126098 in\n              <jats:italic>NELL1<\/jats:italic>\n              (MAF=40.98% in cases and 32.07% in controls;\n              <jats:italic>P=<\/jats:italic>\n              2.40\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              8, OR=1.53), rs2390325 between\n              <jats:italic>PKN2<\/jats:italic>\n              and\n              <jats:italic>LMO4<\/jats:italic>\n              (MAF=21.19% in cases and 15.12% in controls;\n              <jats:italic>P<\/jats:italic>\n              =1.92\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              7, OR=1.62), and rs270065 in\n              <jats:italic>CSMD1<\/jats:italic>\n              (MAF=33.63% in cases and 40.25% in controls;\n              <jats:italic>P<\/jats:italic>\n              =9.51\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              7, OR=0.69). Note that the associations of idiopathic VT for\n              <jats:italic>CCR7<\/jats:italic>\n              variant rs78960694 and\n              <jats:italic>NELL1<\/jats:italic>\n              variant rs68126098 reach genome-wide significance (\n              <jats:italic>P<\/jats:italic>\n              &lt;5.00\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              8). Overexpression of either\n              <jats:italic>PKN2<\/jats:italic>\n              or\n              <jats:italic>CCR7<\/jats:italic>\n              increased the heart rate in zebrafish, and enhanced expression of\n              <jats:italic>CACNA1C, RYR2<\/jats:italic>\n              , or\n              <jats:italic>NOS1AP<\/jats:italic>\n              in zebrafish embryos, HEK293, and AC16 cardiomyocytes. Overexpression of either\n              <jats:italic>PKN2<\/jats:italic>\n              or\n              <jats:italic>CCR7<\/jats:italic>\n              significantly increased L-type Ca2+ current density.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              The first genome-wide association study identifies 4 novel loci and 2 risk genes (\n              <jats:italic>PKN2<\/jats:italic>\n              and\n              <jats:italic>CCR7<\/jats:italic>\n              ) for idiopathic VT. These findings identify new molecular determinants for cardiac calcium homeostasis and rhythm maintenance and provide novel targets for diagnosis and treatment for idiopathic VT.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.121.003603","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T15:40:47Z","timestamp":1658936447000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Genome-Wide Association Study for Idiopathic Ventricular Tachyarrhythmias Identifies Key Role of\n            <i>CCR7<\/i>\n            and\n            <i>PKN2<\/i>\n            in Calcium Homeostasis and Cardiac Rhythm Maintenance"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0189-618X","authenticated-orcid":true,"given":"Chen","family":"Fang","sequence":"first","affiliation":[{"name":"The Center for Human Genome Research, Key Laboratory of 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(C.F., P.W., D.Y., X.Z., D.G.,L.L., X.B., W.X., H.L., Y.Y., X.R., T.K., X.T., C.X., Q.K.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan (C.F., P.W., D.Y., X.Z., D.G.,L.L., X.B., W.X., H.L., Y.Y., X.R., T.K., X.T., C.X., Q.K.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzhi","family":"Gou","sequence":"additional","affiliation":[{"name":"The Center for Human Genome Research, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan (C.F., P.W., D.Y., X.Z., D.G.,L.L., X.B., W.X., H.L., Y.Y., X.R., T.K., X.T., C.X., 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