• A frameshift deletion in the sarcomere gene MYL4 causes early-onset familial atrial fibrillation.

      Gudbjartsson, Daniel F; Holm, Hilma; Sulem, Patrick; Masson, Gisli; Oddsson, Asmundur; Magnusson, Olafur Th; Saemundsdottir, Jona; Helgadottir, Hafdis Th; Helgason, Hannes; Johannsdottir, Hrefna; et al. (Oxford University Press, 2017-01-01)
      Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substantial morbidity and mortality with a major worldwide public health impact. It is increasingly recognized as a highly heritable condition. This study aimed to determine genetic risk factors for early-onset AF.
    • Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.

      Cho, Yoon Shin; Chen, Chien-Hsiun; Hu, Cheng; Long, Jirong; Ong, Rick Twee Hee; Sim, Xueling; Takeuchi, Fumihiko; Wu, Ying; Go, Min Jin; Yamauchi, Toshimasa; et al. (Nature Pub. Group, 2012-01)
      We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
    • A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke.

      Gudbjartsson, Daniel F; Holm, Hilma; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Walters, G Bragi; Thorgeirsson, Gudmundur; Gulcher, Jeffrey; Mathiesen, Ellisiv B; Njølstad, Inger; Nyrnes, Audhild; et al. (2009-08-01)
      We expanded our genome-wide association study on atrial fibrillation (AF) in Iceland, which previously identified risk variants on 4q25, and tested the most significant associations in samples from Iceland, Norway and the United States. A variant in the ZFHX3 gene on chromosome 16q22, rs7193343-T, associated significantly with AF (odds ratio OR = 1.21, P = 1.4 x 10(-10)). This variant also associated with ischemic stroke (OR = 1.11, P = 0.00054) and cardioembolic stroke (OR = 1.22, P = 0.00021) in a combined analysis of five stroke samples.
    • Variants conferring risk of atrial fibrillation on chromosome 4q25.

      Gudbjartsson, Daniel F; Arnar, David O; Helgadottir, Anna; Gretarsdottir, Solveig; Holm, Hilma; Sigurdsson, Asgeir; Jonasdottir, Adalbjorg; Baker, Adam; Thorleifsson, Gudmar; Kristjansson, Kristleifur; et al. (Nature Publishing Group, 2007-07-19)
      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.