{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:00:17Z","timestamp":1790611217469,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              To better define the importance of the amyloidogenic p.V142I\n              <jats:italic toggle=\"yes\">TTR<\/jats:italic>\n              allele across the life span of a carrier, we leveraged data from All of Us to provide a generalizable assessment of the population-level burden of cardiovascular risk and estimate the age at disease onset.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We included self-identifying Black participants in All of Us who provided genomic data (N=77\u2009767). The exposure of interest was p.V142I\n              <jats:italic toggle=\"yes\">TTR<\/jats:italic>\n              carrier status (N=2213). Outcomes included incident heart failure (HF), atrial fibrillation, and carpal tunnel syndrome.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              The median (interquartile range) age at enrollment was 56 (42\u201364) years. For the subset with genetic ancestry data (N=50\u2009516), the p.V142I\n              <jats:italic toggle=\"yes\">TTR<\/jats:italic>\n              carrier frequency was 3.5% (N=1771) among those with African ancestry. After adjustment for age and traditional risk factors, p.V142I\n              <jats:italic toggle=\"yes\">TTR<\/jats:italic>\n              carrier status was associated with a greater risk of HF (odds ratio, 1.56 [95% CI, 1.22\u20131.99];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.001), atrial fibrillation (odds ratio, 1.3 [95% CI, 1.08\u20131.90];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.013), and carpal tunnel syndrome (odds ratio, 1.94 [95% CI, 1.43\u20132.63];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001).The risks increased in the sixth decade of life. In carriers, the attributable risk of the variant for HF, atrial fibrillation, and carpal tunnel syndrome was 27%, 26%, and 43%, respectively. While traditional HF risk factors did not modify the association of carrier status with HF (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              -interaction &gt;0.05 for all), their presence substantially augmented the risk of HF over a lifetime.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              p.V142I\n              <jats:italic toggle=\"yes\">TTR<\/jats:italic>\n              carriers are at an increased risk of HF and atrial fibrillation, beginning during the sixth decade of life. HF risk rises in a dose-dependent manner with other nonamyloid-related HF risk factors, highlighting the importance of aggressive treatment of HF risk factors among carriers. These observations also confirm the clinical relevance of the p.V142I\n              <jats:italic toggle=\"yes\">TTR<\/jats:italic>\n              variant for individuals of African ancestry and underscore the importance of efforts to increase diagnoses, implement TTR-targeted therapies, and evaluate screening strategies for variant transthyretin cardiac amyloidosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.124.004911","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T09:00:10Z","timestamp":1753261210000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Risk for Heart Failure and Atrial Fibrillation Across the Lifespan for Carriers of the Amyloidogenic p.V142I\n            <i>TTR<\/i>\n            Variant"],"prefix":"10.1161","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2400-3196","authenticated-orcid":true,"given":"Justin L.","family":"Grodin","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-7360","authenticated-orcid":true,"given":"Anand","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6121-7727","authenticated-orcid":true,"suffix":"Jr","given":"Ishan","family":"Rison","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7720-2290","authenticated-orcid":true,"given":"Julia","family":"Kozlitina","sequence":"additional","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development (J.K.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-2150","authenticated-orcid":true,"given":"Lorena","family":"Saelices-Gomez","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Neurodegenerative Diseases, Department of Biophysics, Peter O\u2019Donnell Jr. Brain Institute (L.S.-G.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4784-4513","authenticated-orcid":true,"given":"Saket","family":"Girotra","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-4451","authenticated-orcid":true,"given":"Amil M.","family":"Shah","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-8315","authenticated-orcid":true,"given":"Lori R.","family":"Roth","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Medical University of South Carolina, Charleston (J.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3054-4757","authenticated-orcid":true,"given":"Mark H.","family":"Drazner","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-735X","authenticated-orcid":true,"given":"W.H. Wilson","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Cleveland Clinic, OH (W.H.W.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-5008","authenticated-orcid":true,"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Cardiac Amyloidosis Program, Columbia University Irving Medical Center, New York Presbyterian Hospital (M.S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-7261","authenticated-orcid":true,"given":"James A.","family":"de Lemos","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center (I.R., J.L.G., A.G., S.G., A.M.S., L.R.R., M.H.D., J.A.L.), Dallas."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.596"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2023.09.016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.4467"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.17935"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2021.09.015"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1404852"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2021.09.006"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.2896"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.01.042"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.6623"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.028973"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.04.042"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0234962"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1809937"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06957-x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0508-491"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.07.092"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2021.06.022"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.121.013829"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2020.04.019"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2023.1525"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/13506129.2018.1556156"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.14622"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/17531934231218997"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22876-9"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2023.11.016"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3109\/13506129.2015.1051219"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2010.02.006"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.124.004911","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T18:00:31Z","timestamp":1755626431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.124.004911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1161\/CIRCGEN.124.004911"],"URL":"https:\/\/doi.org\/10.1161\/circgen.124.004911","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2024-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}