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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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

In: European Journal of Human Genetics, Vol. 32, 2024, p. 215–223.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Senftleber, NK, Andersen, MK, Jørsboe, E, Stæger, FF, Nøhr, AK, Garcia-Erill, G, Meisner, J, Santander, CG, Balboa, RF, Gilly, A, Bjerregaard, P, Larsen, CVL, Grarup, N, Jørgensen, ME, Zeggini, E, Moltke, I, Hansen, T & Albrechtsen, A 2024, 'GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal', European Journal of Human Genetics, vol. 32, pp. 215–223. https://doi.org/10.1038/s41431-023-01485-8

APA

Senftleber, N. K., Andersen, M. K., Jørsboe, E., Stæger, F. F., Nøhr, A. K., Garcia-Erill, G., Meisner, J., Santander, C. G., Balboa, R. F., Gilly, A., Bjerregaard, P., Larsen, C. V. L., Grarup, N., Jørgensen, M. E., Zeggini, E., Moltke, I., Hansen, T., & Albrechtsen, A. (2024). GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal. European Journal of Human Genetics, 32, 215–223. https://doi.org/10.1038/s41431-023-01485-8

Vancouver

Senftleber NK, Andersen MK, Jørsboe E, Stæger FF, Nøhr AK, Garcia-Erill G et al. GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal. European Journal of Human Genetics. 2024;32:215–223. https://doi.org/10.1038/s41431-023-01485-8

Author

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. / GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal. In: European Journal of Human Genetics. 2024 ; Vol. 32. pp. 215–223.

Bibtex

@article{60caeaf9bead443398823ba9dcb74ead,
title = "GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal",
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. [Figure not available: see fulltext.].",
author = "Senftleber, {Ninna Karsb{\ae}k} and Andersen, {Mette K.} and Emil J{\o}rsboe and St{\ae}ger, {Frederik Filip} and N{\o}hr, {Anne Krogh} and Genis Garcia-Erill and Jonas Meisner and Santander, {Cindy G.} and Balboa, {Renzo F.} and Arthur Gilly and Peter Bjerregaard and Larsen, {Christina Viskum Lytken} and Niels Grarup and J{\o}rgensen, {Marit Eika} and Eleftheria Zeggini and Ida Moltke and Torben Hansen and Anders Albrechtsen",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2024",
doi = "10.1038/s41431-023-01485-8",
language = "English",
volume = "32",
pages = "215–223",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal

AU - Senftleber, Ninna Karsbæk

AU - Andersen, Mette K.

AU - Jørsboe, Emil

AU - Stæger, Frederik Filip

AU - Nøhr, Anne Krogh

AU - Garcia-Erill, Genis

AU - Meisner, Jonas

AU - Santander, Cindy G.

AU - Balboa, Renzo F.

AU - Gilly, Arthur

AU - Bjerregaard, Peter

AU - Larsen, Christina Viskum Lytken

AU - Grarup, Niels

AU - Jørgensen, Marit Eika

AU - Zeggini, Eleftheria

AU - Moltke, Ida

AU - Hansen, Torben

AU - Albrechtsen, Anders

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2024

Y1 - 2024

N2 - 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. [Figure not available: see fulltext.].

AB - 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. [Figure not available: see fulltext.].

U2 - 10.1038/s41431-023-01485-8

DO - 10.1038/s41431-023-01485-8

M3 - Journal article

C2 - 37903942

AN - SCOPUS:85175247548

VL - 32

SP - 215

EP - 223

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

ER -

ID: 372814758