Forskning
Udskriv Udskriv
Switch language
Bispebjerg Hospital - en del af Københavns Universitetshospital
Udgivet

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Alcohol Intake and Total Mortality in 142,960 Individuals from the MORGAM Project: a population-based study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Tre ønsker for 2022: Mere og bedre fokus på populationer, samarbejder og brug af data.

    Publikation: Bidrag til tidsskriftBidrag til avis - KronikFormidling

  3. Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. The power of genetic diversity in genome-wide association studies of lipids

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. The age-specific incidence of type 2 diabetes in Danish elderly adults – the role of size at birth

    Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

  • Lifelines Cohort authors
Vis graf over relationer

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.

METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration.

RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable.

CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

OriginalsprogEngelsk
Artikelnummer240
TidsskriftBMC Cardiovascular Disorders
Vol/bind19
Udgave nummer1
Sider (fra-til)240
ISSN1471-2261
DOI
StatusUdgivet - 29 okt. 2019

ID: 58249073