Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry
Open accessAbstract
We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.3 x 10(-7)). We replicated this association in an independent cohort from the German AF Network (odds ratio = 1.44; P = 1.6 x 10(-11); combined RR = 1.25; combined P = 1.8 x 10(-15)).
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The 12 SNPs in the AF-GRS are all the SNPs that have been reported to be associated with AF at a genome-wide significance level (P<5×10−8).
“These are all the SNPs that have been reported to be associated with AF at a genome-wide significance level (P<5×10−8), including 4 SNPs at PITX2 locus.18-23”
From Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke (2014) · cites this paper as [20]
The AF-GRS comprises 12 SNPs that had been previously shown to be associated with AF at genome-wide significance.
“The AF-GRS comprised 12 SNPs that had been previously shown to be associated with AF at genome-wide significance.”
From Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke (2014) · cites this paper as [20]
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- Authors
- Benjamin, E. J., Rice, K. M., Arking, D. E., Pfeufer, A., van Noord, C., Smith, A. V., Schnabel, R. B., Bis, J. C., Boerwinkle, E., Sinner, M. F., Dehghan, A., Lubitz, S. A., D'Agostino Sr, R. B., Lumley, T., Ehret, G. B., Heeringa, J., Aspelund, T., Newton-Cheh, C., Larson, M. G., Marciante, K. D., Soliman, E. Z., Rivadeneira, F., Wang, T. J., Eiríksdottir, G., Levy, D., Psaty, B. M., Li, M., Chamberlain, A. M., Hofman, A., Vasan, R. S., Harris, T. B., Rotter, J. I., Kao, W. H. L., Agarwal, S. K., Stricker, B. H. C., Wang, K., Launer, L. J., Smith, N. L., Chakravarti, A., Uitterlinden, A. G., Wolf, P. A., Sotoodehnia, N., Köttgen, A., van Duijn, C. M., Meitinger, T., Mueller, M., Perz, S., Steinbeck, G., Wichmann, H.-E., Lunetta, K. L., Heckbert, S. R., Gudnason, V., Alonso, A., Kääb, S., Ellinor, P. T., & Witteman, J. C. M.
- Affiliations
- Framingham Heart Study (US)
- University of Washington (US)
- Johns Hopkins University (US)
- TUM Klinikum (DE)
- Icelandic Heart Association (IS)
- Johannes Gutenberg University Mainz (DE)
- The University of Texas Health Science Center at Houston (US)
- Ludwig-Maximilians-Universität München (DE)
- Erasmus MC (NL)
- Brigham and Women's Hospital (US)
- University of Iceland (IS)
- Boston University (US)
- Wake Forest University Health Sciences (US)
- Harvard University (US)
- Group Health Cooperative (US)
- University of Minnesota (US)
- National Institutes of Health (US)
- Cedars-Sinai Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Helmholtz Munich (DE)
- Corresponding author
- Benjamin, Emelia J
- Witteman, Jacqueline C M
- ORCID
- Benjamin, Emelia J
- Rice, Kenneth M
- Arking, Dan E
- Smith, Albert V
- Schnabel, Renate B
- Bis, Joshua C
- Boerwinkle, Eric
- Sinner, Moritz F
- Dehghan, Abbas
- Lubitz, Steven A
- Ehret, Georg B
- Aspelund, Thor
- Larson, Martin G
- Soliman, Elsayed Z
- Rivadeneira, Fernando
- Wang, Thomas J
- Levy, Daniel
- Psaty, Bruce M
- Li, Man
- Chamberlain, Alanna M
- Vasan, Ramachandran S
- Harris, Tamara B
- Rotter, Jerome I
- Kao, W H Linda
- Agarwal, Sunil K
- Stricker, Bruno H Ch
- Launer, Lenore J
- Smith, Nicholas L
- Chakravarti, Aravinda
- Uitterlinden, André G
- Wolf, Philip A
- Köttgen, Anna
- Meitinger, Thomas
- Steinbeck, Gerhard
- Wichmann, H-Erich
- Lunetta, Kathryn L
- Heckbert, Susan R
- Gudnason, Vilmundur
- Kääb, Stefan
- Ellinor, Patrick T
- Venue
- Nature Genetics
- Published
- 2009-07-13
- Volume
- 41
- Issue
- 8
- Pages
- 879-881
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2761746
- OpenAlex
- W2063172243
- Cited by
- 390
- References
- 14
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 11 · 2023: 16 · 2022: 6 · 2021: 18 · 2020: 18 · 2019: 17 · 2018: 17 · 2017: 33 · 2016: 26 · 2015: 29 · 2014: 40 · 2013: 33 · 2012: 30
- FWCI
- 23.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (911-03-012, 175.010.200)
- National Institutes of Health (n01hc085082-026, n01hc085081-021, n01hc045133-001, n01ag12100-57-0-2, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01hc55021-47-0-1, n01hc085085-011, n01hc085083-027, n01hc55020-39-0-0, n01hc085080-026, n01hc55016-37-0-0, n01hc055022-024, n01hc085086-022, n01hc55019-35-0-1, n01hc55018-38-0-1, n01hc25195-41-0-1, n01hc55222-0-0-0, n02hl64278-6-0-0, n01hc075150-004, n01hc035129-010, 5r01hl080124-05, n01hc55015-48-0-1)
- National Institute on Aging (N01-AG012100, R01AG028321)
- National Heart, Lung, and Blood Institute (R01-HL080124, N01 HC085086, N01 HC055016, N01 HC085079, N01 HC085083, R01HL088456, N01 HC085080, R01HL087652, N01 HC055020, N01 HC035129, N02 HL064278, R01HL093328, R01HL104156, N01 HC055018, N01 HC015103, N01 HC085085, N01-HC-025195, R01HL087641, N01 HC055022, R01HL059367, N01HC085082, U01HL080295, R01HL076784, N01 HC055019, N01 HC055222, N01 HC085081, T32HL007575, N01 HC075150, N01 HC055021, N01 HC085084, N01 HC055015, N01 HC045133, R01HL092577, R01HL086694)
- National Human Genome Research Institute (U01HG004402)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK033651, P30DK063491)
- National Institute of Neurological Disorders and Stroke (R01NS017950)
- National Center for Research Resources (UL1RR025005, M01RR000069, M01RR000425)
- 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
- atrial fibrillation, ZFHX3, genetic susceptibility, genome-wide association study, European ancestry, CHARGE consortium, replication
- MeSH terms
- Atrial Fibrillation, Chromosomes, Human, Pair 16, Humans, Mutation, Meta-Analysis as Topic, Reproducibility of Results, Homeodomain Proteins, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study
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