{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:05:53Z","timestamp":1790859953439,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The Helix Research Network program is a large population genomics initiative that screens an all-comers population of patients for Centers for Disease Control and Prevention Tier 1 genetic conditions, including familial hypercholesterolemia (FH). We evaluated changes in clinical management and low-density lipoprotein cholesterol (LDL-C) levels among patients we identified to have FH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Participants across 9 US health systems provided samples that underwent clinical-grade exome sequencing. Individuals with a positive screening result for a Tier 1 condition were offered no-cost genetic counseling through their health system. Using medication and laboratory testing records, we evaluated changes in patients\u2019 lipid-lowering therapies and LDL-C levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 228\u2009602 adults enrolled between 2017 to 2025, 1155 (\u22481\/198) had a pathogenic FH variant in\n                      <jats:italic toggle=\"yes\">LDLR<\/jats:italic>\n                      (74%),\n                      <jats:italic toggle=\"yes\">APOB<\/jats:italic>\n                      (25%), or\n                      <jats:italic toggle=\"yes\">PCSK9<\/jats:italic>\n                      (1%). Of the 622 with retrospective and prospective electronic health record data available (mean of 11.8 and 2.1 years, respectively), 84% lacked a prior clinical FH diagnosis. Overall, 33% received new\/modified lipid-lowering therapy within the first year, but this proportion was higher in those with a newly documented FH diagnosis code (57% versus 17% for those without documentation;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Patients with new\/modified therapies had a mean LDL-C reduction of 52 mg\/dL, compared with 20 mg\/dL in patients with no therapeutic change (difference=32 mg\/dL;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Following genetic screening, many patients with a pathogenic FH variant experienced improvements in clinical management and LDL-C levels. Electronic health record documentation of the diagnosis code was associated with a greater likelihood of therapeutic modifications, which, in turn, were associated with larger LDL-C reductions. Findings underscore the powerful potential of population genomic screening for supporting optimal lipid management in individuals with FH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005206","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T10:00:32Z","timestamp":1762336832000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Population Genomic Screening and Improved Lipid Management in Patients With Familial Hypercholesterolemia"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2164-1726","authenticated-orcid":true,"given":"Matthew E.","family":"Levy","sequence":"first","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-787X","authenticated-orcid":true,"given":"Kelly M.","family":"Schiabor Barrett","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7308-103X","authenticated-orcid":true,"given":"Megan N.","family":"Betts","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Diseases, WellSpan Health, Ephrata, PA (M.N.B., D.K., C.A.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kann","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Diseases, WellSpan Health, Ephrata, PA (M.N.B., D.K., C.A.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-2766","authenticated-orcid":true,"given":"Alexandre","family":"Bolze","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9870-5819","authenticated-orcid":true,"given":"Basil","family":"Khuder","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Telis","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0500-9173","authenticated-orcid":true,"given":"Lisa M.","family":"McEwen","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-7786","authenticated-orcid":true,"given":"Amy C.","family":"Sturm","sequence":"additional","affiliation":[{"name":"The Ohio State University Wexner Medical Center, Columbus (A.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7581-5333","authenticated-orcid":true,"given":"Chad","family":"Haldeman-Englert","sequence":"additional","affiliation":[{"name":"Cone Health Precision Health, Greensboro, NC (C.H.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5175-1902","authenticated-orcid":true,"given":"Jeremy","family":"Cauwels","sequence":"additional","affiliation":[{"name":"Sanford Health, Sioux Falls, SD (J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-4324","authenticated-orcid":true,"given":"Douglas","family":"Stoller","sequence":"additional","affiliation":[{"name":"University of Nebraska Medical Center, Omaha (D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-8827","authenticated-orcid":true,"given":"C. Anwar A.","family":"Chahal","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Diseases, WellSpan Health, Ephrata, PA (M.N.B., D.K., C.A.A.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher N.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine, St. Luke\u2019s University Health Network, Bethlehem, PA (C.N.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley A.","family":"Waring","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of South Carolina, Charleston (A.A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Olson","sequence":"additional","affiliation":[{"name":"HealthPartners, Minneapolis, MN (D.A.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2646-8958","authenticated-orcid":true,"given":"Joseph J.","family":"Grzymski","sequence":"additional","affiliation":[{"name":"University of Nevada, School of Medicine, Reno (J.J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8936-9143","authenticated-orcid":true,"given":"Nicole L.","family":"Washington","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9582-4413","authenticated-orcid":true,"given":"William","family":"Lee","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7808-2809","authenticated-orcid":true,"given":"Elizabeth T.","family":"Cirulli","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-4540","authenticated-orcid":true,"given":"Catherine","family":"Hajek","sequence":"additional","affiliation":[{"name":"Helix, San Mateo, CA (M.E.L., K.M.S.B., A.B., B.K., N.T., L.M.M., N.L.W., W.L., E.T.C., C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013225"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.044"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0836"},{"key":"e_1_3_3_5_2","volume-title":"GeneReviews(\u00ae)","author":"Ison HE","year":"1993","unstructured":"Ison HE, Clarke SL, Knowles JW. Familial hypercholesterolemia. GeneReviews(\u00ae). Seattle (WA): University of Washington, Seattle; 1993."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.11.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.08.014"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.11.014"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0876-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0982-5"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.121.003549"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.025192"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.303.6807.893"},{"key":"e_1_3_3_15_2","unstructured":"WHO Human Genetics Programme. Familial hypercholesterolaemia (FH): report of a second WHO consultation Geneva 4 September 1998. World Health Organization; 1999."},{"key":"e_1_3_3_16_2","unstructured":"Helix Research Network (HRN). ClinicalTrialsGov. 2024. Accessed March 13 2025. https:\/\/clinicaltrials.gov\/study\/NCT06057181"},{"key":"e_1_3_3_17_2","unstructured":"Centers for Disease Control and Prevention. Tier 1 genomic applications toolkit for public health departments. 2014. Accessed February 12 2025. https:\/\/archive.cdc.gov\/#\/details?url=https:\/\/www.cdc.gov\/genomics\/implementation\/toolkit\/index.htm"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14288-y"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jamia\/ocu023"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2021.09.012"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00870-7"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2024.100284"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.163.1.65"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34368"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.125.005206","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T19:00:40Z","timestamp":1765911640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.125.005206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1161\/CIRCGEN.125.005206"],"URL":"https:\/\/doi.org\/10.1161\/circgen.125.005206","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}