GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal
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, trigly...
Published in: | European Journal of Human Genetics |
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Main Authors: | , , , , , , , , , , , , , , , , , |
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Language: | English |
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2024
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Online Access: | https://curis.ku.dk/portal/da/publications/gwas-of-lipids-in-greenlanders-finds-association-signals-shared-with-europeans-and-reveals-an-independent-pcsk9-association-signal(60caeaf9-bead-4433-9882-3ba9dcb74ead).html https://doi.org/10.1038/s41431-023-01485-8 https://curis.ku.dk/ws/files/381502771/s41431_023_01485_8_2_.pdf |
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ftcopenhagenunip:oai:pure.atira.dk:publications/60caeaf9-bead-4433-9882-3ba9dcb74ead 2024-06-09T07:46:30+00:00 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 2024 application/pdf https://curis.ku.dk/portal/da/publications/gwas-of-lipids-in-greenlanders-finds-association-signals-shared-with-europeans-and-reveals-an-independent-pcsk9-association-signal(60caeaf9-bead-4433-9882-3ba9dcb74ead).html https://doi.org/10.1038/s41431-023-01485-8 https://curis.ku.dk/ws/files/381502771/s41431_023_01485_8_2_.pdf eng eng info:eu-repo/semantics/openAccess 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 , vol. 32 , pp. 215–223 . https://doi.org/10.1038/s41431-023-01485-8 article 2024 ftcopenhagenunip https://doi.org/10.1038/s41431-023-01485-8 2024-05-16T11:29:31Z 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. 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 ... Article in Journal/Newspaper greenlander* greenlandic University of Copenhagen: Research European Journal of Human Genetics 32 2 215 223 |
institution |
Open Polar |
collection |
University of Copenhagen: Research |
op_collection_id |
ftcopenhagenunip |
language |
English |
description |
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. 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 ... |
format |
Article in Journal/Newspaper |
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 |
spellingShingle |
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 |
author_facet |
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 |
author_sort |
Senftleber, Ninna Karsbæk |
title |
GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal |
title_short |
GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal |
title_full |
GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal |
title_fullStr |
GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal |
title_full_unstemmed |
GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal |
title_sort |
gwas of lipids in greenlanders finds association signals shared with europeans and reveals an independent pcsk9 association signal |
publishDate |
2024 |
url |
https://curis.ku.dk/portal/da/publications/gwas-of-lipids-in-greenlanders-finds-association-signals-shared-with-europeans-and-reveals-an-independent-pcsk9-association-signal(60caeaf9-bead-4433-9882-3ba9dcb74ead).html https://doi.org/10.1038/s41431-023-01485-8 https://curis.ku.dk/ws/files/381502771/s41431_023_01485_8_2_.pdf |
genre |
greenlander* greenlandic |
genre_facet |
greenlander* greenlandic |
op_source |
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 , vol. 32 , pp. 215–223 . https://doi.org/10.1038/s41431-023-01485-8 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.1038/s41431-023-01485-8 |
container_title |
European Journal of Human Genetics |
container_volume |
32 |
container_issue |
2 |
container_start_page |
215 |
op_container_end_page |
223 |
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1801376355358605312 |