Dataset Information

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

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.

SUBMITTER: Norby FL

PROVIDER: S-EPMC4801208 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

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

Norby Faye L FL Eryd Samuel Adamsson SA Niemeijer Maartje N MN Rose Lynda M LM Smith Albert V AV Yin Xiaoyan X Agarwal Sunil K SK Arking Dan E DE Chasman Daniel L DL Chen Lin Y LY Eijgelsheim Mark M Engström Gunnar G Franco Oscar H OH Heeringa Jan J Hindy George G Hofman Albert A Lutsey Pamela L PL Magnani Jared W JW McManus David D DD Orho-Melander Marju M Pankow James S JS Rukh Gull G Schulz Christina-Alexandra CA Uitterlinden André G AG Albert Christine M CM Benjamin Emelia J EJ Gudnason Vilmundur V Smith J Gustav JG Stricker Bruno H C BH Alonso Alvaro A

PloS one 20160321 3

<h4>Background</h4>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.<h4>Methods</h4>We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based ...[more]

PMID: 26999784

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Project description:ImportanceAlthough rare variants in cardiac ion channels, transcription factors, and myocardial structural proteins are associated with early-onset atrial fibrillation (AF) in White individuals of European descent, it remains unclear whether genetic variation also contributes to the cause of AF in those of minority ethnicity.ObjectivesTo assess the prevalence of rare and novel pathogenic variants in candidate genes in ethnic minority probands with early-onset AF and determine genotype-phenotype associations.Design, setting, and participantsIn this cohort, family-based study, probands of African and Hispanic descent with early-onset AF (defined as AF occurring in individuals aged ≤66 years) prospectively enrolled in a clinical and genetic biorepository underwent sequencing of 60 candidate genes. Recruitment took place from July 1, 2015, to June 30, 2019. Data were analyzed from February 1 to February 28, 2020.ExposuresRare and novel variants categorized as pathogenic or likely pathogenic.Main outcomes and measuresThe prevalence of rare and novel pathogenic variants in African American and Hispanic/Latinx probands with early-onset AF and genotype-phenotype associations.ResultsAmong 227 probands with early-onset AF, mean (SD) age at onset of AF was 51.0 (9.9) years, 132 probands (58.1%) were men, 148 (65.2%) were African American, and 79 (34.8%) were Hispanic/Latinx. A family history of AF was verified in 24 probands with early-onset AF (10.6%). Sequencing 60 candidate genes identified 53 (23 rare and 30 novel) variants with 16 of the 227 (7.0%) probands harboring likely pathogenic (43.8%) or pathogenic (56.2%) variants, with most loss-of-function variants in TTN, the gene encoding the sarcomeric protein titin (46.7%). In 6 families with more than 2 affected members, variants of unknown significance in sodium channel (SCN10A), potassium channel (KCNE5), sarcomeric proteins (MYH6 and TTN), and atrial natriuretic peptide (NPPA) cosegregated with AF.Conclusions and relevanceIn this study, likely pathogenic and pathogenic variants were identified, with most loss-of-function variants in TTN, that increase susceptibility to early-onset AF in African American and Hispanic/Latinx individuals. These findings provide further understanding toward molecular phenotyping of AF and suggest novel mechanism-based therapeutic approaches for this common arrhythmia in ethnic minority groups.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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