{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T15:40:43Z","timestamp":1784994043966,"version":"3.55.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Familial hypercholesterolemia (FH) is a common autosomal codominant genetic disorder, which causes elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Even among individuals with monogenic FH, there is substantial interindividual variability in LDL-C levels and risk of ASCVD. We assessed the influence of an LDL-C polygenic score on levels of LDL-C and risk of ASCVD for individuals with monogenic FH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We constructed a weighted LDL-C polygenic score, composed of 28 single-nucleotide variants, for individuals with monogenic FH from the British Columbia FH (n=262); Nutrition, Metabolism and Atherosclerosis Clinic (n=552); and UK Biobank cohorts (n=306). We assessed the association between LDL-C polygenic score with LDL-C levels and ASCVD risk using linear regression and Cox-proportional hazard models, respectively. ASCVD was defined as myocardial infarction, coronary or carotid revascularization, transient ischemic attack, or stroke. The results from individual cohorts were combined in fixed-effect meta-analyses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Levels of LDL-C were significantly associated with LDL-C polygenic score in the Nutrition, Metabolism and Atherosclerosis Clinic cohort, UK Biobank cohort, and in the meta-analysis (\u03b2 [95% CI]=0.13 [0.072\u20130.19] per a 20% increase in LDL-C polygenic score percentile,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). Additionally, an elevated LDL-C polygenic score (\u226580th percentile) was associated with a trend towards increased ASCVD risk in all 3 cohorts individually. This association was statistically significant in the meta-analysis (hazard ratio [95% CI]=1.48 [1.02\u20132.14],\n              <jats:italic>P<\/jats:italic>\n              =0.04).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Polygenic contributions to LDL-C explain some of the heterogeneity in clinical presentation and ASCVD risk for individuals with FH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.002919","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T19:56:46Z","timestamp":1597348606000},"page":"515-523","source":"Crossref","is-referenced-by-count":57,"title":["Polygenic Contribution to Low-Density Lipoprotein Cholesterol Levels and Cardiovascular Risk in Monogenic Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"13","author":[{"given":"Mark","family":"Trinder","sequence":"first","affiliation":[{"name":"Centre for Heart Lung Innovation (M.T., L.R.B.), University of British Columbia, Vancouver."},{"name":"Experimental Medicine Program (M.T., L.R.B.), University of British Columbia, Vancouver."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Paquette","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montr\u00e9al, Quebec (M.P., A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubomira","family":"Cermakova","sequence":"additional","affiliation":[{"name":"Healthy Heart Program Prevention Clinic, St Paul\u2019s Hospital, Vancouver, British Columbia (L.C., L.R.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Ban","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry and Robarts Research Institute, Western University, London, ON (M.R.B., R.A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":true,"given":"Robert A.","family":"Hegele","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry and Robarts Research Institute, Western University, London, ON (M.R.B., R.A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Baass","sequence":"additional","affiliation":[{"name":"Nutrition, Metabolism and Atherosclerosis Clinic, Institut de recherches cliniques de Montr\u00e9al, Quebec (M.P., A.B.)."},{"name":"Departments of Medicine, McGill University, Montreal, Quebec, Canada (A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-3807","authenticated-orcid":true,"given":"Liam R.","family":"Brunham","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation (M.T., L.R.B.), University of British Columbia, Vancouver."},{"name":"Experimental Medicine Program (M.T., L.R.B.), University of British Columbia, Vancouver."},{"name":"Departments of Medicine and Medical Genetics (L.R.B.), University of British Columbia, Vancouver."},{"name":"Healthy Heart Program Prevention Clinic, St Paul\u2019s Hospital, Vancouver, British Columbia (L.C., 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