| Title: | GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal |
| Journal: | European Journal of Human Genetics |
| Published: | 30 Oct 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37903942/ |
| DOI: | https://doi.org/10.1038/s41431-023-01485-8 |
| URL: | https://www.nature.com/articles/s41431-023-01485-8.pdf |
| Citations: | 3 (3 in last 2 years) as of 8 Aug 2024 |
Publication 9305
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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.</p>
18 Authors
- Ninna Karsbæk Senftleber
- Mette K. Andersen
- Emil Jørsboe
- Frederik Filip Stæger
- Anne Krogh Nøhr
- Genis Garcia-Erill
- Jonas Meisner
- Cindy G. Santander
- Renzo F. Balboa
- Arthur Gilly
- Peter Bjerregaard
- Christina Viskum Lytken Larsen
- Niels Grarup
- Marit Eika Jørgensen
- Eleftheria Zeggini
- Ida Moltke
- Torben Hansen
- Anders Albrechtsen
1 Application
| Application ID | Title |
|---|---|
| 32683 | Combined effect of the genetic and lifestyle determinants of metabolic syndrome on cardiometabolic risk |
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