Common variants associated with plasma triglycerides and risk for coronary artery disease

Ron Do; Cristen J. Willer; Ellen M. Schmidt; Sebanti Sengupta; Chi Gao; Gina M. Peloso; Stefan Gustafsson; Stavroula Kanoni; Andrea Ganna; Jin Chen; Martin L. Buchkovich; Samia Mora; Jacques S. Beckmann; Jennifer L. Bragg-Gresham; Hsing-Yi Chang; Ayse Demirkan; Heleen M. Den Hertog; Louise A. Donnelly; Georg B. Ehret; Tonu Esko; Mary F. Feitosa; Teresa Ferreira; Krista Fischer; Pierre Fontanillas; Ross M. Fraser; Daniel F. Freitag; Deepti Gurdasani; Kauko Heikkila; Elina Hyppoenen; Aaron Isaacs; Anne U. Jackson; Asa Johansson; Toby Johnson; Marika Kaakinen; Johannes Kettunen; Marcus E. Kleber; Xiaohui Li; Jian'an Luan; Leo-Pekka Lyytikainen; Patrik K. E. Magnusson; Massimo Mangino; Evelin Mihailov; May E. Montasser; Martina Mueller-Nurasyid; Ilja M. Nolte; Jeffrey R. O'Connell; Cameron D. Palmer; Markus Perola; Author collaboration

doi:10.1038/ng.2795

Common variants associated with plasma triglycerides and risk for coronary artery disease

Ron Do, Cristen J. Willer, Ellen M. Schmidt, Sebanti Sengupta, Chi Gao, Gina M. Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L. Buchkovich, Samia Mora, Jacques S. Beckmann, Jennifer L. Bragg-Gresham, Hsing-Yi Chang, Ayse Demirkan, Heleen M. Den Hertog, Louise A. Donnelly, Georg B. Ehret, Tonu EskoMary F. Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M. Fraser, Daniel F. Freitag, Deepti Gurdasani, Kauko Heikkila, Elina Hyppoenen, Aaron Isaacs, Anne U. Jackson, Asa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E. Kleber, Xiaohui Li, Jian'an Luan, Leo-Pekka Lyytikainen, Patrik K. E. Magnusson, Massimo Mangino, Evelin Mihailov, May E. Montasser, Martina Mueller-Nurasyid, Ilja M. Nolte, Jeffrey R. O'Connell, Cameron D. Palmer, Markus Perola, Author collaboration

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Original language	English
Pages (from-to)	1345-1352
Number of pages	9
Journal	Nature Genetics
Volume	45
Issue number	11
DOIs	https://doi.org/10.1038/ng.2795
Publication status	Published - Nov 2013
Externally published	Yes

Keywords

High-density-lipoprotein
Mendelian randomization
Heart-disease
Cardiovascular-disease
Genetic epidemiology
Cholesterol levels
Loci
Contribute
Therapy

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10.1038/ng.2795

Cite this

Do, R., Willer, C. J., Schmidt, E. M., Sengupta, S., Gao, C., Peloso, G. M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M. L., Mora, S., Beckmann, J. S., Bragg-Gresham, J. L., Chang, H.-Y., Demirkan, A., Den Hertog, H. M., Donnelly, L. A., Ehret, G. B., ... Author collaboration (2013). Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature Genetics, 45(11), 1345-1352. https://doi.org/10.1038/ng.2795

@article{6b75726495bd47d1972bb770d29d143b,

title = "Common variants associated with plasma triglycerides and risk for coronary artery disease",

abstract = "Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.",

keywords = "High-density-lipoprotein, Mendelian randomization, Heart-disease, Cardiovascular-disease, Genetic epidemiology, Cholesterol levels, Loci, Contribute, Therapy",

author = "Ron Do and Willer, {Cristen J.} and Schmidt, {Ellen M.} and Sebanti Sengupta and Chi Gao and Peloso, {Gina M.} and Stefan Gustafsson and Stavroula Kanoni and Andrea Ganna and Jin Chen and Buchkovich, {Martin L.} and Samia Mora and Beckmann, {Jacques S.} and Bragg-Gresham, {Jennifer L.} and Hsing-Yi Chang and Ayse Demirkan and {Den Hertog}, {Heleen M.} and Donnelly, {Louise A.} and Ehret, {Georg B.} and Tonu Esko and Feitosa, {Mary F.} and Teresa Ferreira and Krista Fischer and Pierre Fontanillas and Fraser, {Ross M.} and Freitag, {Daniel F.} and Deepti Gurdasani and Kauko Heikkila and Elina Hyppoenen and Aaron Isaacs and Jackson, {Anne U.} and Asa Johansson and Toby Johnson and Marika Kaakinen and Johannes Kettunen and Kleber, {Marcus E.} and Xiaohui Li and Jian'an Luan and Leo-Pekka Lyytikainen and Magnusson, {Patrik K. E.} and Massimo Mangino and Evelin Mihailov and Montasser, {May E.} and Martina Mueller-Nurasyid and Nolte, {Ilja M.} and O'Connell, {Jeffrey R.} and Palmer, {Cameron D.} and Markus Perola and {Author collaboration}",

year = "2013",

month = nov,

doi = "10.1038/ng.2795",

language = "English",

volume = "45",

pages = "1345--1352",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

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Do, R, Willer, CJ, Schmidt, EM, Sengupta, S, Gao, C, Peloso, GM, Gustafsson, S, Kanoni, S, Ganna, A, Chen, J, Buchkovich, ML, Mora, S, Beckmann, JS, Bragg-Gresham, JL, Chang, H-Y, Demirkan, A, Den Hertog, HM, Donnelly, LA, Ehret, GB, Esko, T, Feitosa, MF, Ferreira, T, Fischer, K, Fontanillas, P, Fraser, RM, Freitag, DF, Gurdasani, D, Heikkila, K, Hyppoenen, E, Isaacs, A, Jackson, AU, Johansson, A, Johnson, T, Kaakinen, M, Kettunen, J, Kleber, ME, Li, X, Luan, J, Lyytikainen, L-P, Magnusson, PKE, Mangino, M, Mihailov, E, Montasser, ME, Mueller-Nurasyid, M, Nolte, IM, O'Connell, JR, Palmer, CD, Perola, M & Author collaboration 2013, 'Common variants associated with plasma triglycerides and risk for coronary artery disease', Nature Genetics, vol. 45, no. 11, pp. 1345-1352. https://doi.org/10.1038/ng.2795

TY - JOUR

T1 - Common variants associated with plasma triglycerides and risk for coronary artery disease

AU - Do, Ron

AU - Willer, Cristen J.

AU - Schmidt, Ellen M.

AU - Sengupta, Sebanti

AU - Gao, Chi

AU - Peloso, Gina M.

AU - Gustafsson, Stefan

AU - Kanoni, Stavroula

AU - Ganna, Andrea

AU - Chen, Jin

AU - Buchkovich, Martin L.

AU - Mora, Samia

AU - Beckmann, Jacques S.

AU - Bragg-Gresham, Jennifer L.

AU - Chang, Hsing-Yi

AU - Demirkan, Ayse

AU - Den Hertog, Heleen M.

AU - Donnelly, Louise A.

AU - Ehret, Georg B.

AU - Esko, Tonu

AU - Feitosa, Mary F.

AU - Ferreira, Teresa

AU - Fischer, Krista

AU - Fontanillas, Pierre

AU - Fraser, Ross M.

AU - Freitag, Daniel F.

AU - Gurdasani, Deepti

AU - Heikkila, Kauko

AU - Hyppoenen, Elina

AU - Isaacs, Aaron

AU - Jackson, Anne U.

AU - Johansson, Asa

AU - Johnson, Toby

AU - Kaakinen, Marika

AU - Kettunen, Johannes

AU - Kleber, Marcus E.

AU - Li, Xiaohui

AU - Luan, Jian'an

AU - Lyytikainen, Leo-Pekka

AU - Magnusson, Patrik K. E.

AU - Mangino, Massimo

AU - Mihailov, Evelin

AU - Montasser, May E.

AU - Mueller-Nurasyid, Martina

AU - Nolte, Ilja M.

AU - O'Connell, Jeffrey R.

AU - Palmer, Cameron D.

AU - Perola, Markus

AU - Author collaboration

PY - 2013/11

Y1 - 2013/11

N2 - Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

AB - Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

KW - High-density-lipoprotein

KW - Mendelian randomization

KW - Heart-disease

KW - Cardiovascular-disease

KW - Genetic epidemiology

KW - Cholesterol levels

KW - Loci

KW - Contribute

KW - Therapy

U2 - 10.1038/ng.2795

DO - 10.1038/ng.2795

M3 - Article

C2 - 24097064

SN - 1061-4036

VL - 45

SP - 1345

EP - 1352

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -