Evidence map›Paper›PMID 29593015›Full record

ArticleCirculation2018

An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels.

May E Montasser, Elizabeth A O'Hare, Xiaochun Wang, Alicia D Howard, Rebecca McFarland, James A Perry, Kathleen A Ryan, Kenneth Rice, Cashell E Jaquish, Alan R Shuldiner and 4 more

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

Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. The dark genome in cardiovascular medicine.European heart journal · 2026
    Review
  2. Article
  3. Article
  4. Exonic Variation and Its Clinical Impact in 7221 Old Order Amish.American journal of medical genetics. Part A · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Pseudogenes in Cardiovascular Disease.Frontiers in molecular biosciences · 2020
    Review
  9. Review
  10. Article
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

14 authors at 1 institution in 1 country.

May E MontasserDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Elizabeth A O'HareDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Xiaochun WangDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Alicia D HowardDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Rebecca McFarlandDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
James A PerryDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Kathleen A RyanDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Kenneth RiceDepartment of Biostatistics, University of Washington, Seattle (K.R.).
Cashell E JaquishDivision of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (C.E.J.).
Alan R ShuldinerDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Michael MillerDivision of Cardiovascular Medicine (M.M.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Braxton D MitchellDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Norann A ZaghloulDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Yen-Pei C ChangDivision of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
United States Department of Veterans Affairs · US

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Edward L Melanson · 1995 to 2026
$32.6M
Research BaseP30DK072488 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D, TAYLOR, SIMEON I. · 2005 to 2019
$17.3M
Genome-wide Search for CVD Gene-Environment InteractionsU01HL072515 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2002 to 2008
$11.2M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Longevity Genes in Founder PopulationsR01AG018728 · NIA · UNIVERSITY OF MARYLAND BALTIMORE · PI SHULDINER, ALAN R. · 2001 to 2005
$3.8M
Identification and Functional characterization of a gene influencing LDL-C on 5qR01HL121007 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2014 to 2017
$3.1M
Basal body regulation of glucose homeostasisR01DK102001 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI MITCHELL, BRAXTON D · 2014 to 2018
$1.7M
NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL121007NHLBI NIH HHS U01 HL072515NIA NIH HHS R01 AG018728NIDDK NIH HHS P30 DK048520NIDDK NIH HHS P30 DK072488NIDDK NIH HHS R01 DK102001
6 · The paper itself

Abstract

backgroundElevated levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease via its contribution to the development and progression of atherosclerotic lesions. Although the genetic basis of LDL-C has been studied extensively, currently known genetic variants account for only ≈20% of the variation in LDL-C levels.

methodsThrough an array-based association analysis in 1102 Amish subjects, we identified a variant strongly associated with LDL-C levels. Using a combination of genetic analyses, zebrafish models, and in vitro experiments, we sought to identify the causal gene driving this association.

resultsWe identified a founder haplotype associated with a 15 mg/dL increase in LDL-C on chromosome 5. After recombination mapping, the associated region contained 8 candidate genes. Using a zebrafish model to evaluate the relevance of these genes to cholesterol metabolism, we found that expression of the transcribed pseudogene, APOOP1, increased LDL-C and vascular plaque formation.

conclusionsBased on these data, we propose that APOOP1 regulates levels of LDL-C in humans, thus identifying a novel mechanism of lipid homeostasis.

Indexed as

Chromosomes, Human, Pair 5PseudogenesAmishAnimalsAnimals, Genetically ModifiedAtherosclerosisCholesterol, LDLDyslipidemiasFounder EffectGenetic Association StudiesGenetic Predisposition to DiseaseHaplotypesHumansPhenotypeRecombination, GeneticRisk FactorsCholesterol, LDLcholesterol, LDLchromosome mappingfounder effectgeneticspseudogenes

Identifiers

PMID29593015
PMCPMC6162188
OpenAlexW2794446848

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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.