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Editor's Note
August 2017

Risk and Consequences of Atrial Fibrillation: It’s in the Jeans, Not the Genes

Author Affiliations
  • 1Department of Medicine and Center for Digital Health, Stanford University School of Medicine, Stanford, California
  • 2Veterans Affairs Palo Alto Health Care System, Palo Alto, California
  • 3Associate Editor, JAMA Cardiology
JAMA Cardiol. 2017;2(8):871. doi:10.1001/jamacardio.2017.1856

The familial heritability and genetic contribution to development of atrial fibrillation (AF) has been well described across a number of candidate genes and polymorphisms. Genetic risk scores have been developed to estimate risk of incident AF, but only minimally improve prediction beyond established AF risk factors.1 This genetic risk score was associated with increased risk of stroke among patients with AF, but established risk factors for stroke, such as the CHA2DS2-VASc score, or concomitant stroke-prevention therapies were not accounted for, which could have overestimated heritability of risk. Moreover, the role of candidate risk score genes in development of AF or sequelae is controversial.

To address these important evidence gaps, Chang and colleagues2 sought to estimate the contribution of heritability of AF and subsequent major adverse cardiovascular events (MACE) at the population-level using administrative health care data that captures virtually the entire population of Taiwan. The authors found that persons with a first-degree relative with AF had a near doubling of relative risk of AF. After matching and adjustment incident, AF patients with and without first-degree relatives with AF had similar MACE-free survival, suggesting that the heritability did not contribute to risk of AF outcomes after accounting for risk factors and treatment. Genetic factors accounted for 20% of the phenotypic variance of development of AF, whereas most of the phenotypic variance (76.6%) was accounted for by non-shared environmental factors. The authors posited that the probability of sporadic, non-heritable AF was 82.8%.

This article is notable for several reasons. First, the authors performed genealogy reconstruction across an entire population, which from a public health standpoint demonstrates the value of the ability to link multiple population-level data sets. At present, this may be difficult to perform in the United States and other countries where a number of barriers exist for data linkage, although comprehensive linkage may be on the horizon. Second, these data confirm that AF, like many other common cardiovascular conditions, is multifactorial, and that the overwhelming majority of the risk is related to risk factors, rather than genetic destiny. Based on randomized trials that have shown improvement in AF severity and often remission, we now recognize that AF, like other forms of cardiovascular disease, is one that can be managed with targeting risk factors, including obesity, hypertension, and sleep apnea.3 While genetics, metabolomics, and systems biology remain important research domains to improve our relatively elementary understanding of AF and its mechanisms, this paper serves as a reminder that, for the overwhelming majority of patients, addressing risk of AF and its sequelae should be more about reducing waist size (fitting into jeans) than being preoccupied with heritability (genes).

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Article Information

Corresponding Author: Mintu P. Turakhia, MD, MAS, Department of Medicine and Center for Digital Health, Stanford University School of Medicine, Stanford, 3801 Miranda Ave, 111C, Palo Alto, CA 94304 (mintu@stanford.edu).

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Disclaimer: The content and opinions expressed are solely the responsibility of the author and do not necessarily represent the views or policies of the Department of Veterans Affairs.

Lubitz  SA, Yin  X, Lin  HJ,  et al; AFGen Consortium.  Genetic risk prediction of atrial fibrillation.  Circulation. 2017;135(14):1311-1320.PubMedGoogle ScholarCrossref
Chang  S-H, Kuo  C-F, Chou  I-J,  et al.  Association of a family history of atrial fibrillation with incidence and outcomes of atrial fibrillation: a population-based family cohort study  [published online July 5, 2017].  JAMA Cardiol. doi:10.1001/jamacardio.2017.1855Google Scholar
Gallagher  C, Hendriks  JML, Mahajan  R,  et al.  Lifestyle management to prevent and treat atrial fibrillation.  Expert Rev Cardiovasc Ther. 2016;14(7):799-809.PubMedGoogle ScholarCrossref