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Association of Rare Protein-Truncating DNA Variants in APOB or PCSK9 With Low-density Lipoprotein Cholesterol Level and Risk of Coronary Heart Disease by Jacqueline S. Dron; Aniruddh P. Patel; Yiyi Zhang; Sean J. Jurgens; Dimitri J. Maamari; Minxian Wang; Eric Boerwinkle; Alanna C. Morrison; Paul S. de Vries; Myriam Fornage; Lifang Hou; Donald M. Lloyd-Jones; Bruce M. Psaty; Russell P. Tracy; Joshua C. Bis; Ramachandran S. Vasan; Daniel Levy; Nancy Heard-Costa; Stephen S. Rich; Xiuqing Guo; Kent D. Taylor; Richard A. Gibbs; Jerome I. Rotter; Cristen J. Willer; Elizabeth C. Oelsner; Andrew E. Moran; Gina M. Peloso; Pradeep Natarajan; Amit V. Khera is a Medicine article available to read on EtoBox.

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Importance Protein-truncating variants (PTVs) in apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) are associated with significantly lower low-density lipoprotein (LDL) cholesterol concentrations. The association of these PTVs with coronary heart disease (CHD) warrants further characterization in large, multiracial prospective cohort studies. Objective To evaluate the association of PTVs in APOB and PCSK9 with LDL cholesterol concentrations and CHD risk. Design, Setting, and Participants This studied included participants from 5 National Heart, Lung, and Blood Institute (NHLBI) studies and the UK Biobank. NHLBI study participants aged 5 to 84 years were recruited between 1971 and 2002 across the US and underwent whole-genome sequencing. UK Biobank participants aged 40 to 69 years were recruited between 2006 and 2010 in the UK and underwent whole-exome sequencing. Data were analyzed from June 2021 to October 2022. Exposures PTVs in APOB and PCSK9. Main Outcomes and Measures Estimated untreated LDL cholesterol levels and CHD. Results Among 19 073 NHLBI participants (10 598 [55.6%] female; mean [SD] age, 52 [17] years), 139 (0.7%) carried an APOB or PCS

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Author

Jacqueline S. Dron; Aniruddh P. Patel; Yiyi Zhang; Sean J. Jurgens; Dimitri J. Maamari; Minxian Wang; Eric Boerwinkle; Alanna C. Morrison; Paul S. de Vries; Myriam Fornage; Lifang Hou; Donald M. Lloyd-Jones; Bruce M. Psaty; Russell P. Tracy; Joshua C. Bis; Ramachandran S. Vasan; Daniel Levy; Nancy Heard-Costa; Stephen S. Rich; Xiuqing Guo; Kent D. Taylor; Richard A. Gibbs; Jerome I. Rotter; Cristen J. Willer; Elizabeth C. Oelsner; Andrew E. Moran; Gina M. Peloso; Pradeep Natarajan; Amit V. Khera

Publisher

American Medical Association (AMA)

Published

2023

Language

EN

Field

Medicine (Health Sciences)