{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:13:28Z","timestamp":1791026008286,"version":"4.1.0"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Electrocardiography is one of the most valuable noninvasive diagnostic tools in determining the presence of many cardiovascular diseases. Genetic factors are important in determining ECG abnormalities and their link to cardiovascular diseases. Genome\u2010wide association studies and polygenic risk scores (PRSs) have been conducted for various ECG traits such as QT interval and QRS duration. However, these studies mainly focused on cohorts of European descent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In this cohort study, genome\u2010wide association studies for 6 ECG traits (RR, PR, corrected QT interval [QTc], QRS, JT, and\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      wave duration) were conducted in a Middle Eastern cohort from the Qatar Precision Health Institute, comprising 13\u2009827 subjects with whole\u2010genome sequence data. Middle Eastern PRSs were developed using clumping and thresholding, and their performance was compared with 26 published PRSs. Genetic predisposition to long QT syndrome was explored using rare variant analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Seventy\u2010four independent loci were obtained with genome\u2010wide significance across the 6 traits (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;5\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Of the 74 loci, 67 (90.5%) were previously reported, and 7 loci (9.5%) were novel and contained 6 genes:\n                      <jats:italic toggle=\"no\">STAC<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"no\">CSMD1<\/jats:italic>\n                      for PR,\n                      <jats:italic toggle=\"no\">ANK1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"no\">NCOA2<\/jats:italic>\n                      for QRS,\n                      <jats:italic toggle=\"no\">LSP1<\/jats:italic>\n                      for QTc, and\n                      <jats:italic toggle=\"no\">MKLN1<\/jats:italic>\n                      for\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      wave duration. All 26 published PRSs showed good performance in our cohort. PGS002276 showed the best performance for QTc (\n                      <jats:italic toggle=\"no\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =0.059,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =4.83\u00d710\n                      <jats:sup>\u2212185<\/jats:sup>\n                      ), PGS002166 showed the best performance for QRS (\n                      <jats:italic toggle=\"no\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =0.024,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =1.53\u00d710\n                      <jats:sup>\u221275<\/jats:sup>\n                      ), and PGS000905 showed the best performance for PR (\n                      <jats:italic toggle=\"no\">R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =0.053,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =2.57\u00d710\n                      <jats:sup>\u2212165<\/jats:sup>\n                      ). Some of these PRSs were associated with cardiovascular diseases. For example, PGS003500, a QTc PRS, was significantly associated with cardiomyopathy (odds ratio per 1 SD=1.58 [95% CI, 1.23\u20132.01];\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =2.42\u00d710\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). Middle Eastern PRSs substantially outperformed published PRSs and did not perform well in the UK Biobank data. Ten pathogenic variants, including 3 that are specific to Qatari individuals, were observed in 17 long QT syndrome genes and were carried by 19 individuals. The QTc average was larger for mutation carriers (415.6\u00b123.5 versus 402.3\u00b118.5 in noncarriers). Five\u2010year follow\u2010up data did not show a significant change in ECG patterns, regardless of mutation status and PRS values. Four of 2302 individuals had prolonged QTc intervals over the 2 time points.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In this first genome\u2010wide association study for ECG traits in the Middle East using whole\u2010genome sequence data, 7 novel loci (6 genes) were identified. Published PRSs performed well, but newly developed Middle Eastern\u2013specific PRSs performed the best. Novel variants in long QT syndrome genes were observed for the first time in Qatari individuals. Follow\u2010up data did not show significant changes in ECG patterns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.038341","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T06:05:19Z","timestamp":1740549919000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Genome\u2010Wide Association Study for Resting Electrocardiogram in the Qatari Population Identifies 6 Novel Genes and Validates Novel Polygenic Risk Scores"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0645-9993","authenticated-orcid":false,"given":"Nahin","family":"Khan","sequence":"first","affiliation":[{"name":"Qatar Computing Research Institute, Hamad Bin Khalifa University","place":["Doha, 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