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

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...

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Vydáno v:PloS one Ročník 11; číslo 3; s. e0151932
Hlavní autoři: Norby, Faye L., Eryd, Samuel Adamsson, Niemeijer, Maartje N., Rose, Lynda M., Smith, Albert V., Yin, Xiaoyan, Agarwal, Sunil K., Arking, Dan E., 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 21.03.2016
Public Library of Science (PLoS)
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ISSN:1932-6203, 1932-6203
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Abstract 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. 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. 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). In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
AbstractList 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.
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. 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. 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). In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
BackgroundSeveral 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.MethodsWe 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.ResultsDuring 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).ConclusionsIn this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
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.BACKGROUNDSeveral 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.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.METHODSWe 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.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).RESULTSDuring 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).In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.CONCLUSIONSIn this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
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 wereidentified. 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.
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.
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. 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. 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). In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.
Audience Academic
Author McManus, David D.
Pankow, James S.
Norby, Faye L.
Hofman, Albert
Niemeijer, Maartje N.
Eijgelsheim, Mark
Orho-Melander, Marju
Chasman, Daniel L.
Chen, Lin Y.
Stricker, Bruno H. C.
Gudnason, Vilmundur
Heeringa, Jan
Engström, Gunnar
Schulz, Christina-Alexandra
Benjamin, Emelia J.
Hindy, George
Smith, J. Gustav
Eryd, Samuel Adamsson
Albert, Christine M.
Lutsey, Pamela L.
Magnani, Jared W.
Arking, Dan E.
Rukh, Gull
Agarwal, Sunil K.
Uitterlinden, André G.
Franco, Oscar H.
Yin, Xiaoyan
Alonso, Alvaro
Rose, Lynda M.
Smith, Albert V.
AuthorAffiliation 7 Cardiology and Preventive Medicine Sections, Department of Biostatistics, Boston University School of Medicine, Boston, Massachusetts, United States of America
15 Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
1 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America
12 Cardiology and Preventive Medicine Sections, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America
16 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America
17 Department of Cardiology, Lund University, Lund, Sweden
2 Department of Clinical Sciences, Lund University, Malmö, Sweden
8 Icahn School of Medicine, Mount Sinai Heart Center, New York, New York, United States of America
18 Inspectorate of Health Ca
AuthorAffiliation_xml – name: 5 Icelandic Heart Association, Research Institute, Kopavogur, Iceland
– name: 10 Cardiac Arrhythmia Center, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America
– name: 4 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
– name: 7 Cardiology and Preventive Medicine Sections, Department of Biostatistics, Boston University School of Medicine, Boston, Massachusetts, United States of America
– name: 18 Inspectorate of Health Care, Utrecht, the Netherlands
– name: 1 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America
– name: 9 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
– name: 12 Cardiology and Preventive Medicine Sections, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America
– name: 6 The University of Iceland, Reykjavik, Iceland
– name: 2 Department of Clinical Sciences, Lund University, Malmö, Sweden
– name: 15 Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
– name: 16 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America
– name: 17 Department of Cardiology, Lund University, Lund, Sweden
– name: 3 Department of Epidemiology, Erasmus Medical Center—University Medical Center, Rotterdam, The Netherlands
– name: University at Buffalo, UNITED STATES
– name: 11 Department of Internal Medicine, Erasmus Medical Center—University Medical Center, Rotterdam, The Netherlands
– name: 13 The National Heart, Lung and Blood Institute’s and Boston University’s Framingham Heart Study, Framingham, Massachusetts, United States of America
– name: 14 Departments of Medicine and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
– name: 8 Icahn School of Medicine, Mount Sinai Heart Center, New York, New York, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26999784$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright COPYRIGHT 2016 Public Library of Science
2016 Norby et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2016 Norby et al 2016 Norby et al
Copyright_xml – notice: COPYRIGHT 2016 Public Library of Science
– notice: 2016 Norby et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2016 Norby et al 2016 Norby et al
CorporateAuthor Institutionen för kliniska vetenskaper, Lund
Sektion II
Lunds universitet
Section II
Profile areas and other strong research environments
Department of Clinical Sciences, Malmö
Lund University
Kardiologi
Department of Clinical Sciences, Lund
Strategiska forskningsområden (SFO)
EpiHealth: Epidemiology for Health
EXODIAB: Excellence of Diabetes Research in Sweden
Faculty of Medicine
Strategic research areas (SRA)
Medicinska fakulteten
Cardiology
Profilområden och andra starka forskningsmiljöer
Institutionen för kliniska vetenskaper, Malmö
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– name: Institutionen för kliniska vetenskaper, Malmö
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– name: Institutionen för kliniska vetenskaper, Lund
– name: Strategic research areas (SRA)
– name: Lunds universitet
– name: Department of Clinical Sciences, Lund
– name: Profilområden och andra starka forskningsmiljöer
– name: Lund University
– name: EXODIAB: Excellence of Diabetes Research in Sweden
– name: Profile areas and other strong research environments
– name: Department of Clinical Sciences, Malmö
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: FLN AA CMA EJB VG JGS BHCS. Analyzed the data: FLN SAE MNN LMR AVS XY. Wrote the paper: FLN AA SAE MNN LMR AVS XY SKA LYC PLL JSP JWM DEA. Analytical assistance: DLC ME GE OHF JH GH AH DDM MOM GR CAS AU.
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Snippet 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...
Background Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood...
BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood...
BackgroundSeveral studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood...
Background Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood...
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SubjectTerms Aged
Analysis
Atrial fibrillation
Atrial Fibrillation - blood
Atrial Fibrillation - genetics
Biology and Life Sciences
Blood
Blood lipids
Cardiac arrhythmia
Cholesterol
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Clinical Medicine
Cohort Studies
Confidence Intervals
Consortia
Female
Fibrillation
Genetic Association Studies
Genetic diversity
Genetic Pleiotropy
Genetic Predisposition to Disease
Genetic variance
Genetic Variation
Health risk assessment
Humans
Incidence
Klinisk medicin
Lipids
Lipids - blood
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Medicine and Health Sciences
Meta-Analysis as Topic
Middle Aged
Multivariate Analysis
Pleiotropy
Preventive medicine
Risk factors
Single-nucleotide polymorphism
Womens health
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Title Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium
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http://dx.doi.org/10.1371/journal.pone.0151932
Volume 11
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