Shang-Hung Chang1,2, Chang-Fu Kuo3,4, I-Jun Chou5, Lai-Chu See6,7, Kuang-Hui Yu4, Shue-Fen Luo4, Lu-Hsiang Huang8, Weiya Zhang3, Michael Doherty3, Ming-Shien Wen1,2, Chi-Tai Kuo1,2, Yung-Hsin Yeh1,2. 1. Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taiwan. 2. College of Medicine, Chang Gung University, Taoyuan, Taiwan. 3. Division of Rheumatology, Orthopedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, England. 4. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 5. Division of Pediatric Neurology, Chang Gung Memorial Hospital, Linkou, Taiwan. 6. Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 7. Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan, Taiwan. 8. Office for Big Data Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Abstract
Importance: The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. Objectives: To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). Design, Setting, and Participants: In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. Main Outcomes and Measures: The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. Results: In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival. Conclusions and Relevance: Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.
Importance: The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. Objectives: To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). Design, Setting, and Participants: In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. Main Outcomes and Measures: The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. Results: In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AFpatients with vs without an affected first-degree relative had similar MACE-free survival. Conclusions and Relevance: Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.
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