Association of lipid-related genetic variants with the incidence of atrial fibrillation: The AFGen consortium

Faye L. Norby, Samuel Adamsson Eryd, Maartje N. Niemeijer, Lynda M. Rose, Albert V. Smith, Xiaoyan Yin, Sunil K. Agarwal, Dan Arking, Daniel L. Chasman, Lin Y. Chen, Mark Eijgelsheim, Gunnar Engström, Oscar H. Franco, Jan Heeringa, George Hindy, Albert Hofman, Pamela L. Lutsey, Jared W. Magnani, David D. McManus, Marju Orho-MelanderJames S. Pankow, Gull Rukh, Christina Alexandra Schulz, André G. Uitterlinden, Christine M. Albert, Emelia J. Benjamin, Vilmundur Gudnason, J. Gustav Smith, Bruno H C Stricker, Alvaro Alonso

Research output: Contribution to journalArticle

Abstract

Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). Conclusions In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.

Original languageEnglish (US)
Article numbere0151932
JournalPLoS One
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2016

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Atrial Fibrillation
Genes
Lipids
incidence
Incidence
lipids
genes
low density lipoprotein cholesterol
high density lipoprotein cholesterol
LDL Cholesterol
HDL Cholesterol
confidence interval
Hazards
Confidence Intervals
blood lipids
ancestry
Blood
atrial fibrillation
cohort studies
Proportional Hazards Models

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Norby, F. L., Eryd, S. A., Niemeijer, M. N., Rose, L. M., Smith, A. V., Yin, X., ... Alonso, A. (2016). Association of lipid-related genetic variants with the incidence of atrial fibrillation: The AFGen consortium. PLoS One, 11(3), [e0151932]. https://doi.org/10.1371/journal.pone.0151932

Association of lipid-related genetic variants with the incidence of atrial fibrillation : The AFGen consortium. / Norby, Faye L.; Eryd, Samuel Adamsson; Niemeijer, Maartje N.; Rose, Lynda M.; Smith, Albert V.; Yin, Xiaoyan; Agarwal, Sunil K.; Arking, Dan; Chasman, Daniel L.; Chen, Lin Y.; Eijgelsheim, Mark; Engström, Gunnar; Franco, Oscar H.; Heeringa, Jan; Hindy, George; Hofman, Albert; Lutsey, Pamela L.; Magnani, Jared W.; McManus, David D.; Orho-Melander, Marju; Pankow, James S.; Rukh, Gull; Schulz, Christina Alexandra; Uitterlinden, André G.; Albert, Christine M.; Benjamin, Emelia J.; Gudnason, Vilmundur; Smith, J. Gustav; Stricker, Bruno H C; Alonso, Alvaro.

In: PLoS One, Vol. 11, No. 3, e0151932, 01.03.2016.

Research output: Contribution to journalArticle

Norby, FL, Eryd, SA, Niemeijer, MN, Rose, LM, Smith, AV, Yin, X, Agarwal, SK, Arking, D, Chasman, DL, Chen, LY, Eijgelsheim, M, Engström, G, Franco, OH, Heeringa, J, Hindy, G, Hofman, A, Lutsey, PL, Magnani, JW, McManus, DD, Orho-Melander, M, Pankow, JS, Rukh, G, Schulz, CA, Uitterlinden, AG, Albert, CM, Benjamin, EJ, Gudnason, V, Smith, JG, Stricker, BHC & Alonso, A 2016, 'Association of lipid-related genetic variants with the incidence of atrial fibrillation: The AFGen consortium', PLoS One, vol. 11, no. 3, e0151932. https://doi.org/10.1371/journal.pone.0151932
Norby, Faye L. ; Eryd, Samuel Adamsson ; Niemeijer, Maartje N. ; Rose, Lynda M. ; Smith, Albert V. ; Yin, Xiaoyan ; Agarwal, Sunil K. ; Arking, Dan ; Chasman, Daniel L. ; Chen, Lin Y. ; Eijgelsheim, Mark ; Engström, Gunnar ; Franco, Oscar H. ; Heeringa, Jan ; Hindy, George ; Hofman, Albert ; Lutsey, Pamela L. ; Magnani, Jared W. ; McManus, David D. ; Orho-Melander, Marju ; Pankow, James S. ; Rukh, Gull ; Schulz, Christina Alexandra ; Uitterlinden, André G. ; Albert, Christine M. ; Benjamin, Emelia J. ; Gudnason, Vilmundur ; Smith, J. Gustav ; Stricker, Bruno H C ; Alonso, Alvaro. / Association of lipid-related genetic variants with the incidence of atrial fibrillation : The AFGen consortium. In: PLoS One. 2016 ; Vol. 11, No. 3.
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abstract = "Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95{\%} confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4{\%}) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95{\%} CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95{\%} CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). Conclusions In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.",
author = "Norby, {Faye L.} and Eryd, {Samuel Adamsson} and Niemeijer, {Maartje N.} and Rose, {Lynda M.} and Smith, {Albert V.} and Xiaoyan Yin and Agarwal, {Sunil K.} and Dan Arking and Chasman, {Daniel L.} and Chen, {Lin Y.} and Mark Eijgelsheim and Gunnar Engstr{\"o}m and Franco, {Oscar H.} and Jan Heeringa and George Hindy and Albert Hofman and Lutsey, {Pamela L.} and Magnani, {Jared W.} and McManus, {David D.} and Marju Orho-Melander and Pankow, {James S.} and Gull Rukh and Schulz, {Christina Alexandra} and Uitterlinden, {Andr{\'e} G.} and Albert, {Christine M.} and Benjamin, {Emelia J.} and Vilmundur Gudnason and Smith, {J. Gustav} and Stricker, {Bruno H C} and Alvaro Alonso",
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T1 - Association of lipid-related genetic variants with the incidence of atrial fibrillation

T2 - The AFGen consortium

AU - Norby, Faye L.

AU - Eryd, Samuel Adamsson

AU - Niemeijer, Maartje N.

AU - Rose, Lynda M.

AU - Smith, Albert V.

AU - Yin, Xiaoyan

AU - Agarwal, Sunil K.

AU - Arking, Dan

AU - Chasman, Daniel L.

AU - Chen, Lin Y.

AU - Eijgelsheim, Mark

AU - Engström, Gunnar

AU - Franco, Oscar H.

AU - Heeringa, Jan

AU - Hindy, George

AU - Hofman, Albert

AU - Lutsey, Pamela L.

AU - Magnani, Jared W.

AU - McManus, David D.

AU - Orho-Melander, Marju

AU - Pankow, James S.

AU - Rukh, Gull

AU - Schulz, Christina Alexandra

AU - Uitterlinden, André G.

AU - Albert, Christine M.

AU - Benjamin, Emelia J.

AU - Gudnason, Vilmundur

AU - Smith, J. Gustav

AU - Stricker, Bruno H C

AU - Alonso, Alvaro

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). Conclusions In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.

AB - Background: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts. Methods: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score. Results: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04). Conclusions In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.

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