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| Title |
Association of Rare Protein-Truncating DNA Variants in APOB or PCSK9 With Low-density Lipoprotein Cholesterol Level and Risk of Coronary Heart Disease
|
|---|---|
| Published in |
JAMA Cardiology, March 2023
|
| DOI | 10.1001/jamacardio.2022.5271 |
| Pubmed ID | |
| Authors |
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 |
| Abstract |
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. To evaluate the association of PTVs in APOB and PCSK9 with LDL cholesterol concentrations and CHD risk. 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. PTVs in APOB and PCSK9. Estimated untreated LDL cholesterol levels and CHD. Among 19 073 NHLBI participants (10 598 [55.6%] female; mean [SD] age, 52 [17] years), 139 (0.7%) carried an APOB or PCSK9 PTV, which was associated with 49 mg/dL (95% CI, 43-56) lower estimated untreated LDL cholesterol level. Over a median (IQR) follow-up of 21.5 (13.9-29.4) years, incident CHD was observed in 12 of 139 carriers (8.6%) vs 3029 of 18 934 noncarriers (16.0%), corresponding to an adjusted hazard ratio of 0.51 (95% CI, 0.28-0.89; P = .02). Among 190 464 UK Biobank participants (104 831 [55.0%] female; mean [SD] age, 57 [8] years), 662 (0.4%) carried a PTV, which was associated with 45 mg/dL (95% CI, 42-47) lower estimated untreated LDL cholesterol level. Estimated CHD risk by age 75 years was 3.7% (95% CI, 2.0-5.3) in carriers vs 7.0% (95% CI, 6.9-7.2) in noncarriers, corresponding to an adjusted hazard ratio of 0.51 (95% CI, 0.32-0.81; P = .004). Among 209 537 individuals in this study, 0.4% carried an APOB or PCSK9 PTV that was associated with less exposure to LDL cholesterol and a 49% lower risk of CHD. |
X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 26 | 13% |
| Canada | 4 | 2% |
| United Kingdom | 2 | 1% |
| Finland | 2 | 1% |
| Uganda | 1 | <1% |
| Norway | 1 | <1% |
| Saudi Arabia | 1 | <1% |
| Netherlands | 1 | <1% |
| Pakistan | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 157 | 80% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 103 | 53% |
| Scientists | 56 | 29% |
| Practitioners (doctors, other healthcare professionals) | 32 | 16% |
| Science communicators (journalists, bloggers, editors) | 5 | 3% |
Mendeley readers
The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 18 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Doctoral Student | 2 | 11% |
| Student > Master | 2 | 11% |
| Researcher | 2 | 11% |
| Professor | 1 | 6% |
| Other | 1 | 6% |
| Other | 2 | 11% |
| Unknown | 8 | 44% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 2 | 11% |
| Biochemistry, Genetics and Molecular Biology | 1 | 6% |
| Nursing and Health Professions | 1 | 6% |
| Business, Management and Accounting | 1 | 6% |
| Psychology | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 11 | 61% |
Attention Score in Context
This research output has an Altmetric Attention Score of 135. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 February 2024.
All research outputs
#330,371
of 26,617,554 outputs
Outputs from JAMA Cardiology
#293
of 2,250 outputs
Outputs of similar age
#7,931
of 433,935 outputs
Outputs of similar age from JAMA Cardiology
#8
of 52 outputs
Altmetric has tracked 26,617,554 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,250 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 93.9. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 433,935 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 52 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.