Evidence map›Paper›PMID 35460704›Full record

ArticleJournal of lipid research2022

Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia.

Weilai Dong, Karen H Y Wong, Youbin Liu, Michal Levy-Sakin, Wei-Chien Hung, Mo Li, Boyang Li, Sheng Chih Jin, Jungmin Choi, Francesc Lopez-Giraldez and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of lipid research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 5 countries.

Weilai DongDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Karen H Y WongCardiovascular Research Institute, University of California, San Francisco, CA, USA.
Youbin LiuDepartment of Cardiology, The Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Michal Levy-SakinCardiovascular Research Institute, University of California, San Francisco, CA, USA.
Wei-Chien HungDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Mo LiDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Boyang LiDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Sheng Chih JinDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Jungmin ChoiDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Korea.
Francesc Lopez-GiraldezDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Dedeepya VakaInstitute for Human Genetics, University of California, San Francisco, CA, USA.
Annie PoonInstitute for Human Genetics, University of California, San Francisco, CA, USA.
Catherine ChuInstitute for Human Genetics, University of California, San Francisco, CA, USA.
Richard LaoInstitute for Human Genetics, University of California, San Francisco, CA, USA.
Melek BalamirDepartment of Internal Medicine, Istanbul University, Istanbul, Turkey.
Irina MovsesyanCardiovascular Research Institute, University of California, San Francisco, CA, USA.
Mary J MalloyCardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Pediatrics, University of California, San Francisco, CA, USA.
Hongyu ZhaoDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Pui-Yan KwokCardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Dermatology, University of California, San Francisco, CA, USA.
John P KaneCardiovascular Research Institute, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
Richard P LiftonDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Clive R PullingerCardiovascular Research Institute, University of California, San Francisco, CA, USA; Physiological Nursing, University of California, San Francisco, CA, USA. Electronic address: clive.pullinger@ucsf.edu.
University of California, San Francisco · USYale University · USGuangzhou Eighth People's Hospital · CNIstanbul University · TRKorea University · KRWashington University in St. Louis · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0M
Single molecule DNA mapping for genome and CNV analysisR01HG005946 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KWOK, PUI-YAN, XIAO, MING · 2010 to 2021
$6.5M
NCATS NIH HHS UL1 TR001863NHGRI NIH HHS R01 HG005946NHGRI NIH HHS U54 HG006504Wellcome Trust
6 · The paper itself

Abstract

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4-36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those with the highest prevalence of damaging variants were ABCA1 (n = 20), STAB1 (n = 9), OSBPL1A (n = 8), CPS1 (n = 8), CD36 (n = 7), LRP1 (n = 6), ABCA8 (n = 6), GOT2 (n = 5), AMPD3 (n = 5), WWOX (n = 4), and IRS1 (n = 4). Binomial analysis for damaging missense or loss-of-function variants identified the ABCA1 and LDLR genes at genome-wide significance. In conclusion, whole-exome sequencing of individuals with low HDL-C showed the burden of damaging rare variants in the ABCA1 and LDLR genes is particularly high and revealed numerous occurrences in HDL candidate genes, including many genes identified in genome-wide association study reports. Many of these genes are involved in cancer biology, which accords with epidemiologic findings of the association of HDL deficiency with increased risk of cancer, thus presenting a new area of interest in HDL genomics.

Indexed as

Genome-Wide Association StudyHypoalphalipoproteinemiasCholesterol, HDLExome SequencingHeterozygoteHumansCholesterol, HDLdyslipidemiageneticsHDLLDLlipoproteinsprebeta-1 HDLreverse cholesterol transporttriglycerides

Identifiers

PMID35460704
PMCPMC9126845
OpenAlexW4224274565

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.