Evidence map›Paper›PMID 28772107›Full record

ArticleAtherosclerosis2017

Family-specific aggregation of lipid GWAS variants confers the susceptibility to familial hypercholesterolemia in a large Austrian family.

Elina Nikkola, Arthur Ko, Marcus Alvarez, Rita M Cantor, Kristina Garske, Elliot Kim, Stephanie Gee, Alejandra Rodriguez, Reinhard Muxel, Niina Matikainen and 10 more

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

Article in Atherosclerosis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Trial
  2. Article
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  4. Review
  5. Review
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

20 authors at 9 institutions in 5 countries.

Elina NikkolaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Arthur KoDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA; Molecular Biology Institute at UCLA, Los Angeles, USA.
Marcus AlvarezDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Rita M CantorDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Kristina GarskeDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Elliot KimDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Stephanie GeeDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Alejandra RodriguezDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Reinhard MuxelGeneral Practice Centre, Austria.
Niina MatikainenEndocrinology, Abdominal Centre, Helsinki University Hospital, Finland; Heart and Lung Center, Helsinki University Hospital, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland.
Sanni SöderlundHeart and Lung Center, Helsinki University Hospital, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland.
Mahdi M MotazackerDepartment of Clinical Genetics, Academic Medical Center at the University of Amsterdam, The Netherlands.
Jan BorénDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, University of Gothenburg and Sahlgrenska University Hospital, Sweden.
Claudia LaminaDivision of Genetic Epidemiology, Medical University of Innsbruck, Austria.
Florian KronenbergDivision of Genetic Epidemiology, Medical University of Innsbruck, Austria.
Wolfgang J SchneiderDepartment Medical Biochemistry, Medical University Vienna and Max F. Perutz Laboratories, Austria.
Aarno PalotieInstitute for Molecular Medicine, University of Helsinki, Finland; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Massachusetts General Hospital, Boston, MA, USA.
Markku LaaksoInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Marja-Riitta TaskinenHeart and Lung Center, Helsinki University Hospital, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland.
Päivi PajukantaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, USA; Molecular Biology Institute at UCLA, Los Angeles, USA; Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA. Electronic address: ppajukanta@mednet.ucla.edu.
University of California, Los Angeles · USHelsinki University Hospital · FIInnsbruck Medical University · ATAcademic Medical Center · NLKuopio University Hospital · FIMassachusetts General Hospital · USMax Perutz Labs · ATSahlgrenska University Hospital · SEUniversity of Helsinki · FI

Funding

Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CANTOR, RITA M. · 1985 to 2019
$50.2M
Genomics of dyslipidemia in MexicansR01HL095056 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PAJUKANTA, PAIVI · 2009 to 2018
$5.9M
Identification of lipid biomarkers via integrative genomic approaches in Hispanic populationsF31HL127921 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KO, ARTHUR · 2016 to 2018
$82k
NHLBI NIH HHS F31 HL127921NHLBI NIH HHS P01 HL028481NHLBI NIH HHS R01 HL095056
6 · The paper itself

Abstract

BACKGROUND AND

aimsHypercholesterolemia confers susceptibility to cardiovascular disease (CVD). Both serum total cholesterol (TC) and LDL-cholesterol (LDL-C) exhibit a strong genetic component (heritability estimates 0.41-0.50). However, a large part of this heritability cannot be explained by the variants identified in recent extensive genome-wide association studies (GWAS) on lipids. Our aim was to find genetic causes leading to high LDL-C levels and ultimately CVD in a large Austrian family presenting with what appears to be autosomal dominant inheritance for familial hypercholesterolemia (FH).

methodsWe utilized linkage analysis followed by whole-exome sequencing and genetic risk score analysis using an Austrian multi-generational family with various dyslipidemias, including elevated TC and LDL-C, and one family branch with elevated lipoprotein (a) (Lp(a)).

resultsWe did not find evidence for genome-wide significant linkage for LDL-C or apparent causative variants in the known FH genes rather, we discovered a particular family-specific combination of nine GWAS LDL-C SNPs (p = 0.02 by permutation), and putative less severe familial hypercholesterolemia mutations in the LDLR and APOB genes in a subset of the affected family members. Separately, high Lp(a) levels observed in one branch of the family were explained primarily by the LPA locus, including short (<23) Kringle IV repeats and rs3798220.

conclusionsTaken together, some forms of FH may be explained by family-specific combinations of LDL-C GWAS SNPs.

Indexed as

MutationPolymorphism, Single NucleotideApolipoprotein B-100AustriaBiomarkersCholesterolDNA Mutational AnalysisExome SequencingFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHeredityHumansHyperlipoproteinemia Type IILipoprotein(a)MaleAPOB protein, humanApolipoprotein B-100BiomarkersCholesterolLDLR protein, humanLipoprotein(a)Receptors, LDLFamilial hypercholesterolemia (FH)Genetic risk score (GRS)LDL cholesterolLipoprotein (a)

Identifiers

PMID28772107
PMCPMC5698088
OpenAlexW2737597556

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.