Variants conferring risk of atrial fibrillation on chromosome 4q25.
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Authors
Gudbjartsson, Daniel FArnar, David O
Helgadottir, Anna
Gretarsdottir, Solveig
Holm, Hilma
Sigurdsson, Asgeir
Jonasdottir, Adalbjorg
Baker, Adam
Thorleifsson, Gudmar
Kristjansson, Kristleifur
Palsson, Arnar
Blondal, Thorarinn
Sulem, Patrick
Backman, Valgerdur M
Hardarson, Gudmundur A
Palsdottir, Ebba
Helgason, Agnar
Sigurjonsdottir, Runa
Sverrisson, Jon T
Kostulas, Konstantinos
Ng, Maggie C Y
Baum, Larry
So, Wing Yee
Wong, Ka Sing
Chan, Juliana C N
Furie, Karen L
Greenberg, Steven M
Sale, Michelle
Kelly, Peter
MacRae, Calum A
Smith, Eric E
Rosand, Jonathan
Hillert, Jan
Ma, Ronald C W
Ellinor, Patrick T
Thorgeirsson, Gudmundur
Gulcher, Jeffrey R
Kong, Augustine
Thorsteinsdottir, Unnur
Stefansson, Kari
Issue Date
2007-07-19
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Nature 2007, 448(7151):353-7Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans and is characterized by chaotic electrical activity of the atria. It affects one in ten individuals over the age of 80 years, causes significant morbidity and is an independent predictor of mortality. Recent studies have provided evidence of a genetic contribution to AF. Mutations in potassium-channel genes have been associated with familial AF but account for only a small fraction of all cases of AF. We have performed a genome-wide association scan, followed by replication studies in three populations of European descent and a Chinese population from Hong Kong and find a strong association between two sequence variants on chromosome 4q25 and AF. Here we show that about 35% of individuals of European descent have at least one of the variants and that the risk of AF increases by 1.72 and 1.39 per copy. The association with the stronger variant is replicated in the Chinese population, where it is carried by 75% of individuals and the risk of AF is increased by 1.42 per copy. A stronger association was observed in individuals with typical atrial flutter. Both variants are adjacent to PITX2, which is known to have a critical function in left-right asymmetry of the heart.Description
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http://www.nature.com/nature/journal/v448/n7151/abs/nature06007.htmlae974a485f413a2113503eed53cd6c53
10.1038/nature06007
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