| Autor: |
Senftleber, Ninna Karsbæk, Andersen, Mette K., Jørsboe, Emil, Stæger, Frederik Filip, Nøhr, Anne Krogh, Garcia-Erill, Genis, Meisner, Jonas, Santander, Cindy G., Balboa, Renzo F., Gilly, Arthur, Bjerregaard, Peter, Larsen, Christina Viskum Lytken, Grarup, Niels, Jørgensen, Marit Eika, Zeggini, Eleftheria, Moltke, Ida, Hansen, Torben, Albrechtsen, Anders |
| Zdroj: |
European Journal of Human Genetics: EJHG; February 2024, Vol. 32 Issue: 2 p215-223, 9p |
| Abstrakt: |
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 PCSK9loss-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 PCSK9across tissues in European data from the GTEx portal, and was located in a predicted regulatory element, supporting a possible causal impact on PCSK9expression. 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. |
| Databáze: |
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