Identification of Disease Genes for Atrial Fibrillation

Project: Research project

Project Details

Description

Atrial fibrillation (AF) is the most common sustained arrhythmia, reaching epidemic proportions in the aging
U.S. population and resulting in significant morbidity, mortality, and socioeconomic burden. Preliminary
studies indicate that idiopathic or lone AF is familial in at least 15% of patients, highlighting the importance
of genetic factors in the pathogenesis of this disorder. The overall objective of this study is to identify
genes for AF by linkage and mutational analyses. The first aim is to determine the chromosomal location
of AF genes by genome-wide linkage analyses. Mapping studies will be carried out in 4 large families with
autosomal dominant AF in which linkage to known loci for AF have been excluded. The second aim is to
identify mutations in candidate genes for AF based on chromosomal location, cardiac expression, and
physiological rationale. Novel genes, once identified, will be screened for additional inherited and de novo
mutations in a cohort of 154 unrelated patients with familial and sporadic AF. The third aim is to determine
the frequency and spectrum of heritable ion channel and nuclear membrane defects in racially-diverse
cohorts with lone AF. The long-term objectives of this work are to gain new insights into molecular
mechanisms of arrhythmogenesis and to improve prediction, prevention, and treatment of AF.
StatusNot started

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