{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:51:41Z","timestamp":1782589901472,"version":"3.54.5"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The clinical implications of a polygenic risk score (PRS) for LDL-C (low-density lipoprotein cholesterol) are not well understood, both within the general population and individuals with familial hypercholesterolemia (FH).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We developed the LDL-C PRS using Least Absolute Shrinkage and Selection Operator regression in 377 286 White British participants from UK Biobank and tested its association with LDL-C according to FH variant carrier status in another 41 748 whole-exome sequenced individuals. Next, we tested for an enrichment of FH variant carriers among individuals with severe hypercholesterolemia and low LDL-C PRS. Last, we contrasted the effect of the LDL-C PRS, measured LDL-C and FH variant carrier status on risk of ischemic heart disease among 3010 cases and 38 738 controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Among the 41 748 whole-exome sequenced White British individuals, 1-SD increase in the LDL-C PRS was associated with elevated LDL-C among both FH variant carriers (0.34 [95% CI, 0.22\u20130.47] mmol\/L) and noncarriers (0.42 [95% CI, 0.42\u20130.43] mmol\/L). Among individuals with severe hypercholesterolemia, FH variant carriers were enriched in those with a low LDL-C PRS (odds ratio, 2.20 [95% CI, 1.66\u20132.71] per SD). Each SD increase in the LDL-C PRS was associated with risk of ischemic heart disease to the comparable magnitude as measured LDL-C (odds ratio, 1.24 [95% CI, 1.20\u20131.29] and odds ratio, 1.15 [95% CI, 1.09\u20131.23], respectively). The LDL-C PRS was not strongly associated with other traditional ischemic heart disease risk factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>An LDL-C PRS could be used to identify individuals with a higher probability of harboring FH variants. The association between ischemic heart disease and the LDL-C PRS was comparable to measured LDL-C, likely because the PRS reflects lifetime exposure to LDL-C levels.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.120.003106","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:57Z","timestamp":1610582457000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Polygenic Risk Score for Low-Density Lipoprotein Cholesterol Is Associated With Risk of Ischemic Heart Disease and Enriches for Individuals With Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8383-7639","authenticated-orcid":true,"given":"Haoyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Biostatistics, and Occupational Health (H.W., S.Z., S.R.B., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."},{"name":"Center for Clinical Epidemiology (H.W., V.F., S.Z., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-4720","authenticated-orcid":true,"given":"Vincenzo","family":"Forgetta","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology (H.W., V.F., S.Z., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics, and Occupational Health (H.W., S.Z., S.R.B., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."},{"name":"Center for Clinical Epidemiology (H.W., V.F., S.Z., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-2509","authenticated-orcid":true,"given":"Sahir R.","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics, and Occupational Health (H.W., S.Z., S.R.B., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."},{"name":"Department of Diagnostic Radiology (S.R.B.) and Department of Human Genetics (J.B.R.), McGill University, Montr\u00e9al, QC, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6795-4760","authenticated-orcid":true,"given":"Guillaume","family":"Par\u00e9","sequence":"additional","affiliation":[{"name":"Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, ON, Canada (G.P.)."},{"name":"Departments of Pathology and Molecular Medicine (G.P.), McMaster University, Hamilton, ON, Canada."},{"name":"Departments of Epidemiology and Biostatistics (G.P.), McMaster University, Hamilton, ON, Canada."},{"name":"Department of Biochemistry (G.P.), McMaster University, Hamilton, ON, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-9086","authenticated-orcid":true,"given":"J. Brent","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics, and Occupational Health (H.W., S.Z., S.R.B., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."},{"name":"Center for Clinical Epidemiology (H.W., V.F., S.Z., J.B.R.), Lady Davis Institute, Jewish General Hospital, Montr\u00e9al, QC, Canada."},{"name":"Department of Diagnostic Radiology (S.R.B.) and Department of Human Genetics (J.B.R.), McGill University, Montr\u00e9al, QC, Canada."},{"name":"Department of Twin Research, King\u2019s College London, United Kingdom (J.B.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32203-7"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67394-1"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61778-4"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.520"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00005"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.05.043"},{"key":"e_1_3_5_8_2","first-page":"725.e5","article-title":"Polygenic risk score predicts prevalence of cardiovascular disease in patients with familial hypercholesterolemia.","volume":"11","author":"Paquette M","year":"2017","unstructured":"Paquette, M, Chong, M, Theriault, S, Dufour, R, Pare, G, Baass, A. 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