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Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium

Norby, Faye L; Eryd, Samuel Adamsson LU ; Niemeijer, Maartje N; Rose, Lynda M; Smith, Albert V; Yin, Xiaoyan; Agarwal, Sunil K; Arking, Dan E; Chasman, Daniel L and Chen, Lin Y, et al. (2016) In PLoS One 11(3).
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... (More)

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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Please use this url to cite or link to this publication:
@misc{45446237-3fa5-49b1-89b2-b219aeae1263,
  abstract     = {<p>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.</p><p>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.</p><p>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).</p><p>CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.</p>},
  author       = {Norby, Faye L and Eryd, Samuel Adamsson and Niemeijer, Maartje N and Rose, Lynda M and Smith, Albert V and Yin, Xiaoyan and Agarwal, Sunil K and Arking, Dan E and Chasman, Daniel L and Chen, Lin Y and Eijgelsheim, Mark and Engström, Gunnar and Franco, Oscar H and Heeringa, Jan and Hindy, George and Hofman, Albert and Lutsey, Pamela L and Magnani, Jared W and McManus, David D and Orho-Melander, Marju and Pankow, James S and Rukh, Gull and Schulz, Christina-Alexandra and Uitterlinden, André G and Albert, Christine M and Benjamin, Emelia J and Gudnason, Vilmundur and Smith, Gustav and Stricker, Bruno H C and Alonso, Alvaro},
  issn         = {1932-6203},
  language     = {eng},
  number       = {3},
  publisher    = {ARRAY(0x9cdb1c0)},
  series       = {PLoS One},
  title        = {Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation : The AFGen Consortium},
  url          = {http://dx.doi.org/10.1371/journal.pone.0151932},
  volume       = {11},
  year         = {2016},
}