Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis

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

Standard

Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis. / Helgadottir, Anna; Thorleifsson, Gudmar; Snaebjarnarson, Audunn; Stefansdottir, Lilja; Sveinbjornsson, Gardar; Tragante, Vinicius; Björnsson, Eyþór; Steinthorsdottir, Valgerdur; Gretarsdottir, Solveig; Helgason, Hannes; Saemundsdottir, Jona; Olafsson, Isleifur; Thune, Jens Jakob; Axelsson Raja, Anna; Ghouse, Jonas; Olesen, Morten Salling; Christensen, Alex; Jacobsen, Rikke Louise; Dowsett, Joseph; Bruun, Mie Topholm; Nielsen, Kaspar; Knowlton, Kirk; Nadauld, Lincoln; Benediktsson, Rafn; Erikstrup, Christian; Pedersen, Ole B; Banasik, Karina; Brunak, Søren; Bundgaard, Henning; Ostrowski, Sisse R; Sulem, Patrick; Arnar, David O; Thorgeirsson, Gudmundur; Thorsteinsdottir, Unnur; Gudbjartsson, Daniel F; Stefansson, Kari; Holm, Hilma; DBDS Genomic Consortium.

In: European Journal of Preventive Cardiology, Vol. 29, No. 18, 2022, p. 2374–2385.

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

Harvard

Helgadottir, A, Thorleifsson, G, Snaebjarnarson, A, Stefansdottir, L, Sveinbjornsson, G, Tragante, V, Björnsson, E, Steinthorsdottir, V, Gretarsdottir, S, Helgason, H, Saemundsdottir, J, Olafsson, I, Thune, JJ, Axelsson Raja, A, Ghouse, J, Olesen, MS, Christensen, A, Jacobsen, RL, Dowsett, J, Bruun, MT, Nielsen, K, Knowlton, K, Nadauld, L, Benediktsson, R, Erikstrup, C, Pedersen, OB, Banasik, K, Brunak, S, Bundgaard, H, Ostrowski, SR, Sulem, P, Arnar, DO, Thorgeirsson, G, Thorsteinsdottir, U, Gudbjartsson, DF, Stefansson, K, Holm, H & DBDS Genomic Consortium 2022, 'Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis', European Journal of Preventive Cardiology, vol. 29, no. 18, pp. 2374–2385. https://doi.org/10.1093/eurjpc/zwac219

APA

Helgadottir, A., Thorleifsson, G., Snaebjarnarson, A., Stefansdottir, L., Sveinbjornsson, G., Tragante, V., Björnsson, E., Steinthorsdottir, V., Gretarsdottir, S., Helgason, H., Saemundsdottir, J., Olafsson, I., Thune, J. J., Axelsson Raja, A., Ghouse, J., Olesen, M. S., Christensen, A., Jacobsen, R. L., Dowsett, J., ... DBDS Genomic Consortium (2022). Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis. European Journal of Preventive Cardiology, 29(18), 2374–2385. https://doi.org/10.1093/eurjpc/zwac219

Vancouver

Helgadottir A, Thorleifsson G, Snaebjarnarson A, Stefansdottir L, Sveinbjornsson G, Tragante V et al. Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis. European Journal of Preventive Cardiology. 2022;29(18):2374–2385. https://doi.org/10.1093/eurjpc/zwac219

Author

Helgadottir, Anna ; Thorleifsson, Gudmar ; Snaebjarnarson, Audunn ; Stefansdottir, Lilja ; Sveinbjornsson, Gardar ; Tragante, Vinicius ; Björnsson, Eyþór ; Steinthorsdottir, Valgerdur ; Gretarsdottir, Solveig ; Helgason, Hannes ; Saemundsdottir, Jona ; Olafsson, Isleifur ; Thune, Jens Jakob ; Axelsson Raja, Anna ; Ghouse, Jonas ; Olesen, Morten Salling ; Christensen, Alex ; Jacobsen, Rikke Louise ; Dowsett, Joseph ; Bruun, Mie Topholm ; Nielsen, Kaspar ; Knowlton, Kirk ; Nadauld, Lincoln ; Benediktsson, Rafn ; Erikstrup, Christian ; Pedersen, Ole B ; Banasik, Karina ; Brunak, Søren ; Bundgaard, Henning ; Ostrowski, Sisse R ; Sulem, Patrick ; Arnar, David O ; Thorgeirsson, Gudmundur ; Thorsteinsdottir, Unnur ; Gudbjartsson, Daniel F ; Stefansson, Kari ; Holm, Hilma ; DBDS Genomic Consortium. / Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis. In: European Journal of Preventive Cardiology. 2022 ; Vol. 29, No. 18. pp. 2374–2385.

Bibtex

@article{3f7e3ca1359b4fdcb5894a4283d58a99,
title = "Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis",
abstract = "BACKGROUND AND AIMS: The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration.METHOD AND RESULTS: We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376,336) and on the outcome from a meta-analysis of five CAD data-sets (187,451 cases and 793,315 controls). Subsequently, we carried out sensitivity and replication analyses.In univariate MR analysis both exposures associated with CAD (βnon-HDL-C = 0.40, P = 2.8 × 10-48 and βapoB = 0.38, P = 1.3 × 10-44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 × 10-5), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five percent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 × 10-4 (0.05/235). Fifty-one variants associated at genome-wide significance.CONCLUSION: Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.",
author = "Anna Helgadottir and Gudmar Thorleifsson and Audunn Snaebjarnarson and Lilja Stefansdottir and Gardar Sveinbjornsson and Vinicius Tragante and Ey{\th}{\'o}r Bj{\"o}rnsson and Valgerdur Steinthorsdottir and Solveig Gretarsdottir and Hannes Helgason and Jona Saemundsdottir and Isleifur Olafsson and Thune, {Jens Jakob} and {Axelsson Raja}, Anna and Jonas Ghouse and Olesen, {Morten Salling} and Alex Christensen and Jacobsen, {Rikke Louise} and Joseph Dowsett and Bruun, {Mie Topholm} and Kaspar Nielsen and Kirk Knowlton and Lincoln Nadauld and Rafn Benediktsson and Christian Erikstrup and Pedersen, {Ole B} and Karina Banasik and S{\o}ren Brunak and Henning Bundgaard and Ostrowski, {Sisse R} and Patrick Sulem and Arnar, {David O} and Gudmundur Thorgeirsson and Unnur Thorsteinsdottir and Gudbjartsson, {Daniel F} and Kari Stefansson and Hilma Holm and {DBDS Genomic Consortium}",
note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.",
year = "2022",
doi = "10.1093/eurjpc/zwac219",
language = "English",
volume = "29",
pages = "2374–2385",
journal = "European Journal of Preventive Cardiology",
issn = "2047-4873",
publisher = "SAGE Publications",
number = "18",

}

RIS

TY - JOUR

T1 - Cholesterol not particle concentration mediates the atherogenic risk conferred by apolipoprotein B particles - A Mendelian randomization analysis

AU - Helgadottir, Anna

AU - Thorleifsson, Gudmar

AU - Snaebjarnarson, Audunn

AU - Stefansdottir, Lilja

AU - Sveinbjornsson, Gardar

AU - Tragante, Vinicius

AU - Björnsson, Eyþór

AU - Steinthorsdottir, Valgerdur

AU - Gretarsdottir, Solveig

AU - Helgason, Hannes

AU - Saemundsdottir, Jona

AU - Olafsson, Isleifur

AU - Thune, Jens Jakob

AU - Axelsson Raja, Anna

AU - Ghouse, Jonas

AU - Olesen, Morten Salling

AU - Christensen, Alex

AU - Jacobsen, Rikke Louise

AU - Dowsett, Joseph

AU - Bruun, Mie Topholm

AU - Nielsen, Kaspar

AU - Knowlton, Kirk

AU - Nadauld, Lincoln

AU - Benediktsson, Rafn

AU - Erikstrup, Christian

AU - Pedersen, Ole B

AU - Banasik, Karina

AU - Brunak, Søren

AU - Bundgaard, Henning

AU - Ostrowski, Sisse R

AU - Sulem, Patrick

AU - Arnar, David O

AU - Thorgeirsson, Gudmundur

AU - Thorsteinsdottir, Unnur

AU - Gudbjartsson, Daniel F

AU - Stefansson, Kari

AU - Holm, Hilma

AU - DBDS Genomic Consortium

N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

PY - 2022

Y1 - 2022

N2 - BACKGROUND AND AIMS: The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration.METHOD AND RESULTS: We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376,336) and on the outcome from a meta-analysis of five CAD data-sets (187,451 cases and 793,315 controls). Subsequently, we carried out sensitivity and replication analyses.In univariate MR analysis both exposures associated with CAD (βnon-HDL-C = 0.40, P = 2.8 × 10-48 and βapoB = 0.38, P = 1.3 × 10-44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 × 10-5), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five percent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 × 10-4 (0.05/235). Fifty-one variants associated at genome-wide significance.CONCLUSION: Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.

AB - BACKGROUND AND AIMS: The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration.METHOD AND RESULTS: We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376,336) and on the outcome from a meta-analysis of five CAD data-sets (187,451 cases and 793,315 controls). Subsequently, we carried out sensitivity and replication analyses.In univariate MR analysis both exposures associated with CAD (βnon-HDL-C = 0.40, P = 2.8 × 10-48 and βapoB = 0.38, P = 1.3 × 10-44). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 × 10-5), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five percent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 × 10-4 (0.05/235). Fifty-one variants associated at genome-wide significance.CONCLUSION: Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.

U2 - 10.1093/eurjpc/zwac219

DO - 10.1093/eurjpc/zwac219

M3 - Journal article

C2 - 36125206

VL - 29

SP - 2374

EP - 2385

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

SN - 2047-4873

IS - 18

ER -

ID: 321785706