Affordable Access

Publisher Website

GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal.

Authors
  • Senftleber, Ninna Karsbæk1, 2
  • Andersen, Mette K3
  • Jørsboe, Emil3, 4, 5
  • Stæger, Frederik Filip2
  • Nøhr, Anne Krogh6
  • Garcia-Erill, Genis2
  • Meisner, Jonas7
  • Santander, Cindy G2
  • Balboa, Renzo F2
  • Gilly, Arthur8
  • Bjerregaard, Peter9
  • Larsen, Christina Viskum Lytken9, 10
  • Grarup, Niels3
  • Jørgensen, Marit Eika1, 9, 11
  • Zeggini, Eleftheria8, 12
  • Moltke, Ida13
  • Hansen, Torben14
  • Albrechtsen, Anders15
  • 1 Clinical Research, Copenhagen University Hospital-Steno Diabetes Center Copenhagen, Herlev, Denmark. , (Denmark)
  • 2 Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 3 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 4 Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom. , (United Kingdom)
  • 5 Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • 6 Center for Clinical Data Science, Department of Clinical Medicine, Aalborg University and Research, Education, and Innovation, Aalborg University Hospital, Aalborg, Denmark. , (Denmark)
  • 7 Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 8 Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. , (Germany)
  • 9 Centre for Public Health in Greenland, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark. , (Denmark)
  • 10 Greenland Center for Health Research, Institute for Health and Nature, University of Greenland, Nuuk, Greenland. , (Greenland)
  • 11 Steno Diabetes Center Greenland, Nuuk, Greenland. , (Greenland)
  • 12 Technical University of Munich (TUM) and Klinikum Rechts der Isar, TUM School of Medicine, Munich, Germany. , (Germany)
  • 13 Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark. [email protected]. , (Denmark)
  • 14 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [email protected]. , (Denmark)
  • 15 Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark. [email protected]. , (Denmark)
Type
Published Article
Journal
European Journal of Human Genetics
Publisher
Springer Nature
Publication Date
Feb 01, 2024
Volume
32
Issue
2
Pages
215–223
Identifiers
DOI: 10.1038/s41431-023-01485-8
PMID: 37903942
Source
Medline
Language
English
License
Unknown

Abstract

Perturbation of lipid homoeostasis is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. We aimed to identify genetic variants affecting lipid levels, and thereby risk of CVD, in Greenlanders. Genome-wide association studies (GWAS) of six blood lipids, triglycerides, LDL-cholesterol, HDL-cholesterol, total cholesterol, as well as apolipoproteins A1 and B, were performed in up to 4473 Greenlanders. For genome-wide significant variants, we also tested for associations with additional traits, including CVD events. We identified 11 genome-wide significant loci associated with lipid traits. Most of these loci were already known in Europeans, however, we found a potential causal variant near PCSK9 (rs12117661), which was independent of the known PCSK9 loss-of-function variant (rs11491147). rs12117661 was associated with lower LDL-cholesterol (βSD(SE) = -0.22 (0.03), p = 6.5 × 10-12) and total cholesterol (-0.17 (0.03), p = 1.1 × 10-8) in the Greenlandic study population. Similar associations were observed in Europeans from the UK Biobank, where the variant was also associated with a lower risk of CVD outcomes. Moreover, rs12117661 was a top eQTL for PCSK9 across tissues in European data from the GTEx portal, and was located in a predicted regulatory element, supporting a possible causal impact on PCSK9 expression. Combined, the 11 GWAS signals explained up to 16.3% of the variance of the lipid traits. This suggests that the genetic architecture of lipid levels in Greenlanders is different from Europeans, with fewer variants explaining the variance. © 2023. The Author(s).

Report this publication

Statistics

Seen <100 times