Association of Severe Hypercholesterolemia and Familial Hypercholesterolemia Genotype With Risk of Coronary Heart Disease

Yiyi Zhang, Jacqueline S. Dron, Brandon K. Bellows, Amit V. Khera, Junxiu Liu, Pallavi P. Balte, Elizabeth C. Oelsner, Sami Samir Amr, Matthew S. Lebo, Anna Nagy, Gina M. Peloso, Pradeep Natarajan, Jerome I. Rotter, Cristen Willer, Eric Boerwinkle, Christie M. Ballantyne, Pamela L. Lutsey, Myriam Fornage, Donald M. Lloyd-Jones, Lifang HouBruce M. Psaty, Joshua C. Bis, James S. Floyd, Ramachandran S. Vasan, Nancy L. Heard-Costa, April P. Carson, Michael E. Hall, Stephen S. Rich, Xiuqing Guo, Dhruv S. Kazi, Sarah D. de Ferranti, Andrew E. Moran

Research output: Contribution to journalArticlepeer-review

3 Scopus citations
Original languageEnglish (US)
Pages (from-to)1556-1559
Number of pages4
JournalCirculation
Volume147
Issue number20
DOIs
StatePublished - May 16 2023

Bibliographical note

Funding Information:
The spouse of Dr Willer works at Regeneron Pharmaceuticals. Dr Carson previously received research support for investigator-initiated work from Amgen, Inc. Dr Psaty serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr Ballantyne receives research support from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Novartis, Regeneron, Roche Diagnostic, National Institutes of Health, the American Heart Association, and the American Diabetes Association. Dr Ballantyne serves as a consultant to Abbott Diagnostics, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, and Sanofi-Synthelabo. Dr Khera is an employee of Verve Therapeutics; has served as a scientific advisor to Amgen, Color Health, Foresite Labs, Illumina, Maze Pharmaceuticals, MedGenome, Navitor Pharmaceuticals, Novartis, Sanofi, Sarepta Therapeutics, Third Rock Therapeutics, and Veritas International; holds equity in Verve Therapeutics, Color Health; and has received research funding from IBM Research. The other authors report no conflicts.

Funding Information:
This work was supported primarily by National Institutes of Health R01HL141823 (Drs Moran and de Ferranti). Funding support was also provided by grants K08HG010155 and U01HG011719 (Dr Khera) from the National Human Genome Research Institute, K24HL159246 (Dr Lutsey), and by grants K23HL130627 and R21HL129924 (Dr Oelsner) to support the harmonization of phenotypic data across the TOPMed cohorts. The funder/sponsor had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Funding Information:
The authors thank the investigators, staff, and participants of all 6 cohorts and the TOPMed Consortium (Trans-Omics in Precision Medicine; https://topmed.nhlbi.nih.gov/topmed-banner-authorship ) for their valuable contributions. They also gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. In addition, the authors thank the CCC (Cross-Cohort Collaboration Consortium) for their promotion and support of this multicohort effort. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The ARIC study (Atherosclerosis Risk in Communities) has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Department of Health and Human Services (contracts 75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, and 75N92022D00005). CARDIA (Coronary Artery Risk Development in Young Adults Study) is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). CARDIA was also partially supported by the Intramural Research Program of the National Institute on Aging and an intra-agency agreement between National Institute on Aging and the NHLBI (AG0005). The CHS (Cardiovascular Health Study) was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and 75N92021D00006 and grants U01HL080295, R01HL105756, R01HL105756, and U01HL130114 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by R01AG023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org . The FHS (Framingham Heart Study) was supported by contracts NO1-HC-25195, HHSN268201500001I, and 75N92019D00031 from the NHLBI and grant supplement R01 HL092577-06S1. The JHS (Jackson Heart Study) is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute on Minority Health and Health Disparities. The authors also thank the staff and participants of the JHS. The MESA (Multi-Ethnic Study of Atherosclerosis) projects are conducted and supported by the NHLBI in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1TR001881, DK063491, and R01HL105756. Phenotype harmonization, data management, sample-identity quality control, and general study coordination were provided by the TOPMed Data Coordinating Center (3R01HL-120393-02S1) and TOPMed MESA Multi-Omics (HHSN2682015000031/HSN26800004). A fill list of participating MESA investigators and institutes can be found at http://www.mesa-nhlbi.org . Molecular data for the TOPMed program were supported by the NHLBI. Core support, including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering, was provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support, including phenotype harmonization, data management, sample-identity quality control, and general program coordination, was provided by the TOPMed Data Coordinating Center (R01HL-120393, U01HL-120393; contract HHSN268201800001I).

Keywords

  • cardiovascular disease
  • familial hypercholesterolemia
  • genotype
  • low-density lipoprotein cholesterol
  • phenotype

PubMed: MeSH publication types

  • Letter
  • Research Support, N.I.H., Extramural

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