Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese
UMass Chan AffiliationsMeyers Primary Care Institute
Department of Quantitative Health Sciences
Department of Medicine
Aged, 80 and over
Asian Continental Ancestry Group
*Chromosomes, Human, Pair 4
European Continental Ancestry Group
*Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
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AbstractOBJECTIVES: This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. BACKGROUND: AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. METHODS: We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). RESULTS: We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. CONCLUSIONS: The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity. Elsevier Inc. All rights reserved.
SourceJ Am Coll Cardiol. 2014 Apr 1;63(12):1200-10. doi: 10.1016/j.jacc.2013.12.015. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/37281
Full author list omitted for brevity. For the full list of authors, see article.
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