Familial aggregation of atrial fibrillation in Iceland
Abstract
AIMS: To examine the heritability of atrial fibrillation (AF) in Icelanders, utilizing a nationwide genealogy database and population-based data on AF. AF is a disorder with a high prevalence, which has been known to cluster in families, but the heritability of the common form has not been well defined. METHODS AND RESULTS: The study population included 5269 patients diagnosed since 1987 and age-sex-matched controls randomly selected from the genealogy database. Kinship coefficients (KC), expressed as genealogical index of familiality (GIF = average KC x 100,000), were calculated before and after exclusion of relatives separated by one to five meiotic events. Risk ratios (RR) were calculated for first- to fifth-degree relatives. The average pairwise GIF among patients with AF was 15.9 (mean GIF for controls 13.9, 95%CI = 13.3, 14.4); this declined to 15.4 (mean GIF for controls 13.6, 95%CI = 13.1, 14.2) after exclusion of relatives separated by one meiosis and to 13.7 (mean GIF for controls 12.6, 95%CI = 12.1, 13.2), 12.7 (mean GIF for controls 11.9, 95%CI = 11.4, 12.4), and 11.3 (mean GIF for controls 10.6, 95%CI = 10.1, 11.1) after exclusion of relatives within two, three, and four meioses, respectively (all P<0.00001). RRs among relative pairs also declined incrementally, from 1.77 in first-degree relatives to 1.36, 1.18, 1.10, and 1.05 in second- through fifth-degree relatives (all P<0.001), consistent with the declining proportion of alleles shared identically by descent. When the analysis was limited to subjects diagnosed with AF before the age of 60, first-degree relatives of the AF cases were nearly five times more likely to have AF than the general population. CONCLUSION: AF shows strong evidence of heritability among unselected patients in Iceland, suggesting that there may be undiscovered genetic variants underlying the risk of the common form of AF.
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Several studies evaluating familial aggregation of AF have reported substantially increased risk of AF in individuals with affected family members.
“Several studies evaluating familial aggregation of AF have reported substantially increased risk of AF in individuals with affected family members.8,9,50–55”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [51]
The evidence for a differential AF risk dependent on the sex of the affected family member is ambiguous.
“The evidence for a differential AF risk dependent on the sex of the affected family member is more ambiguous (Supplementary Table S5).”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [51]
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- Authors
- Arnar, D. O., Thorvaldsson, S., Manolio, T. A., Thorgeirsson, G., Kristjansson, K., Hakonarson, H., & Stefansson, K.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-01-20
- Volume
- 27
- Issue
- 6
- Pages
- 708-712
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2122436921
- Cited by
- 305
- References
- 32
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 13 · 2023: 10 · 2022: 2 · 2021: 7 · 2020: 15 · 2019: 13 · 2018: 7 · 2017: 26 · 2016: 28 · 2015: 12 · 2014: 24 · 2013: 21 · 2012: 25
- FWCI
- 12.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- familial aggregation, heritability, genealogical databases, kinship coefficient, relative risk, first-degree relatives, Icelanders
- MeSH terms
- Aged, Atrial Fibrillation, Family Health, Female, Humans, Iceland, Male, Middle Aged, Pedigree, Risk Factors, Cohort Studies, Case-Control Studies, Genetic Predisposition to Disease
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