An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention

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

Standard

An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention. / Jørsboe, Emil; Andersen, Mette K.; Skotte, Line; Stæger, Frederik F.; Færgeman, Nils J.; Hanghøj, Kristian; Santander, Cindy G.; Senftleber, Ninna K.; Diaz, Lars J.; Overvad, Maria; Waples, Ryan K.; Geller, Frank; Bjerregaard, Peter; Melbye, Mads; Larsen, Christina V.L.; Feenstra, Bjarke; Anders Koch, Koch; Jørgensen, Marit E.; Grarup, Niels; Moltke, Ida; Albrechtsen, Anders; Hansen, Torben.

In: Human Genetics and Genomics Advances, Vol. 3, No. 4, 100118, 2022.

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

Harvard

Jørsboe, E, Andersen, MK, Skotte, L, Stæger, FF, Færgeman, NJ, Hanghøj, K, Santander, CG, Senftleber, NK, Diaz, LJ, Overvad, M, Waples, RK, Geller, F, Bjerregaard, P, Melbye, M, Larsen, CVL, Feenstra, B, Anders Koch, K, Jørgensen, ME, Grarup, N, Moltke, I, Albrechtsen, A & Hansen, T 2022, 'An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention', Human Genetics and Genomics Advances, vol. 3, no. 4, 100118. https://doi.org/10.1016/j.xhgg.2022.100118

APA

Jørsboe, E., Andersen, M. K., Skotte, L., Stæger, F. F., Færgeman, N. J., Hanghøj, K., Santander, C. G., Senftleber, N. K., Diaz, L. J., Overvad, M., Waples, R. K., Geller, F., Bjerregaard, P., Melbye, M., Larsen, C. V. L., Feenstra, B., Anders Koch, K., Jørgensen, M. E., Grarup, N., ... Hansen, T. (2022). An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention. Human Genetics and Genomics Advances, 3(4), [100118]. https://doi.org/10.1016/j.xhgg.2022.100118

Vancouver

Jørsboe E, Andersen MK, Skotte L, Stæger FF, Færgeman NJ, Hanghøj K et al. An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention. Human Genetics and Genomics Advances. 2022;3(4). 100118. https://doi.org/10.1016/j.xhgg.2022.100118

Author

Jørsboe, Emil ; Andersen, Mette K. ; Skotte, Line ; Stæger, Frederik F. ; Færgeman, Nils J. ; Hanghøj, Kristian ; Santander, Cindy G. ; Senftleber, Ninna K. ; Diaz, Lars J. ; Overvad, Maria ; Waples, Ryan K. ; Geller, Frank ; Bjerregaard, Peter ; Melbye, Mads ; Larsen, Christina V.L. ; Feenstra, Bjarke ; Anders Koch, Koch ; Jørgensen, Marit E. ; Grarup, Niels ; Moltke, Ida ; Albrechtsen, Anders ; Hansen, Torben. / An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention. In: Human Genetics and Genomics Advances. 2022 ; Vol. 3, No. 4.

Bibtex

@article{3b66fe894cc8415e8b077173b1b6c16f,
title = "An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention",
abstract = "The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18–1.92], p = 0.00096), peripheral artery disease (1.69 [1.01–2.82], p = 0.046), and coronary operations (1.78 [1.21–2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.",
keywords = "cardiovascular disease, genetics, ischemic heart disease, LDL cholesterol, population medicine, precision medicine",
author = "Emil J{\o}rsboe and Andersen, {Mette K.} and Line Skotte and St{\ae}ger, {Frederik F.} and F{\ae}rgeman, {Nils J.} and Kristian Hangh{\o}j and Santander, {Cindy G.} and Senftleber, {Ninna K.} and Diaz, {Lars J.} and Maria Overvad and Waples, {Ryan K.} and Frank Geller and Peter Bjerregaard and Mads Melbye and Larsen, {Christina V.L.} and Bjarke Feenstra and {Anders Koch}, Koch and J{\o}rgensen, {Marit E.} and Niels Grarup and Ida Moltke and Anders Albrechtsen and Torben Hansen",
note = "Publisher Copyright: {\textcopyright} 2022",
year = "2022",
doi = "10.1016/j.xhgg.2022.100118",
language = "English",
volume = "3",
journal = "Human Genetics and Genomics Advances",
issn = "2666-2477",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention

AU - Jørsboe, Emil

AU - Andersen, Mette K.

AU - Skotte, Line

AU - Stæger, Frederik F.

AU - Færgeman, Nils J.

AU - Hanghøj, Kristian

AU - Santander, Cindy G.

AU - Senftleber, Ninna K.

AU - Diaz, Lars J.

AU - Overvad, Maria

AU - Waples, Ryan K.

AU - Geller, Frank

AU - Bjerregaard, Peter

AU - Melbye, Mads

AU - Larsen, Christina V.L.

AU - Feenstra, Bjarke

AU - Anders Koch, Koch

AU - Jørgensen, Marit E.

AU - Grarup, Niels

AU - Moltke, Ida

AU - Albrechtsen, Anders

AU - Hansen, Torben

N1 - Publisher Copyright: © 2022

PY - 2022

Y1 - 2022

N2 - The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18–1.92], p = 0.00096), peripheral artery disease (1.69 [1.01–2.82], p = 0.046), and coronary operations (1.78 [1.21–2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.

AB - The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18–1.92], p = 0.00096), peripheral artery disease (1.69 [1.01–2.82], p = 0.046), and coronary operations (1.78 [1.21–2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.

KW - cardiovascular disease

KW - genetics

KW - ischemic heart disease

KW - LDL cholesterol

KW - population medicine

KW - precision medicine

U2 - 10.1016/j.xhgg.2022.100118

DO - 10.1016/j.xhgg.2022.100118

M3 - Journal article

C2 - 36267056

AN - SCOPUS:85140005806

VL - 3

JO - Human Genetics and Genomics Advances

JF - Human Genetics and Genomics Advances

SN - 2666-2477

IS - 4

M1 - 100118

ER -

ID: 324173743