Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

Tsai, Chia Ti; Hsieh, Chia Shan; Chang, Sheng‐Nan; Chuang, Eric Y.; Juang, Jyh-Ming Jimmy; Lin, Lian Yu; Lai, Ling‐Ping; Hwang, Juey‐Jen; Chiang, Fu-Tien; Lin, Jiunn Lee

doi:10.1136/jmedgenet-2014-102618

Cited by 43 publications

(22 citation statements)

References 36 publications

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“…To circumvent some of these problems, updated versions of candidate gene studies have been proposed where instead of screening whole genomes, they choose to deep-sequence specific genes that have been previously identified through GWAS. This approach has a much higher resolution and has been useful for detecting new strong-effect variants (Zuk et al, 2014; Tsai et al, 2015). Nevertheless, these approaches still not provide a definite solution for the missing heritability problem.…”

Section: Introduction: Gwas and The Missing Heritability Problemmentioning

confidence: 99%

The Human Microbiome and the Missing Heritability Problem

et al. 2017

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The “missing heritability” problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this “missing heritability” have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies.

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Section: Introduction: Gwas and The Missing Heritability Problemmentioning

confidence: 99%

The Human Microbiome and the Missing Heritability Problem

et al. 2017

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“…As only a minority of athletes with a history of vigorous endurance sports develops AF, the question remains open, which factors finally determine the arrhythmogenic risk of the athletes’ atria. Genomewide association studies have identified common variants in nine genomic regions associated with AF . Even though genetic predisposition is one probable risk‐modifying factor, to our knowledge, no typical genetic mutation has been identified in athletes with AF so far.…”

Section: Discussionmentioning

confidence: 99%

Excess of exercise increases the risk of atrial fibrillation

Müssigbrodt

Weber

Mandrola

et al. 2017

Scandinavian Med Sci Sports

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An interesting and still not well-understood example for old medical wisdom "Sola dosis facit venenum" is the increased prevalence of atrial fibrillation (AF) in athletes. Numerous studies have shown a fourfold to eightfold increased risk of AF in athletes compared to the normal population. Analysis of the existing data suggests a dose-dependent effect of exercise. Moderate exercise seems to have a protective effect and decreases the risk of AF, whereas excessive exercise seems to increase the risk of AF. The described cases illustrate clinical manifestations within the spectrum of AF in elderly athletes, that is, exercise-induced AF, vagal AF, chronic AF, and atrial flutter. As the arrhythmia worsened quality of life and exercise capacity in all patients, recovery of sinus rhythm was desired in all described cases. As the atrial disease was advanced on different levels, different treatment regimes were applied. Lifestyle modification and temporary anti-arrhythmic drug therapy could stabilize sinus rhythm in one patient, whereas others needed radiofrequency ablation to achieve a stable sinus rhythm. The patient with the most advanced atrial disease necessitated anti-arrhythmic drug therapy and another left atrial ablation. All described patients remained in sinus rhythm during the long-term follow-up.

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“…The genes mentioned above, CLPG, STAT3, STAT5A, POU1F1 and PROP1, all have SNPs associated with growth traits, and some SNP genotypes were found to be significantly associated with mRNA expression levels (Jia et al, 2015;Lan et al, 2007Lan et al, , 2009Wu et al, 2014;Zhao et al, 2013). In humans, functional SNPs that were associated with disease were found in the ATBF1 gene (Liu et al, 2014;Tsai et al, 2015). Moreover, four SNPs that were significantly associated with goat growth traits were identified in the goat ATBF1 gene (Zhang et al, 2015b).…”

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confidence: 91%

Evaluation of novel SNPs and haplotypes within the <i>ATBF1</i> gene and their effects on economically important production traits in cattle

Zhang

et al. 2017

Arch. Anim. Breed.

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Abstract. AT motif binding factor 1 (ATBF1) gene can promote the expression level of the growth hormone 1 (GH1) gene by binding to the enhancers of the POU1F1 and PROP1 genes; thus, it affects the growth and development of livestock. Considering that the ATBF1 gene also has a close relationship with the Janus kinasesignal transductor and activator of transcription (JAK-STAT) pathway, the objective of this work was to identify novel single-nucleotide polymorphism (SNP) variations and their association with growth traits in native Chinese cattle breeds. Five novel SNPs within the ATBF1 gene were found in 644 Qinchuan and Jinnan cattle for first time using 25 pairs of screening and genotyping primers. The five novel SNPs were named as AC_000175:g.140344C>G (SNP1), g.146573T>C (SNP2), g.205468C>T (SNP3), g.205575A>G (SNP4) and g.297690C

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Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

Abstract: The genetic architecture of subjects with extreme phenotypes of AF is similar to that of rare or Mendelian diseases, and mutations may be the underlying cause.

Cited by 43 publications

References 36 publications

The Human Microbiome and the Missing Heritability Problem

The Human Microbiome and the Missing Heritability Problem

Excess of exercise increases the risk of atrial fibrillation

Evaluation of novel SNPs and haplotypes within the <i>ATBF1</i> gene and their effects on economically important production traits in cattle

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Next-generation sequencing of nine atrial fibrillation candidate genes identified novel de novo mutations in patients with extreme trait of atrial fibrillation

Abstract: The genetic architecture of subjects with extreme phenotypes of AF is similar to that of rare or Mendelian diseases, and mutations may be the underlying cause.

Cited by 43 publications

References 36 publications

The Human Microbiome and the Missing Heritability Problem

The Human Microbiome and the Missing Heritability Problem

Excess of exercise increases the risk of atrial fibrillation

Evaluation of novel SNPs and haplotypes within the &lt;i&gt;ATBF1&lt;/i&gt; gene and their effects on economically important production traits in cattle

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Product

Resources

About

Evaluation of novel SNPs and haplotypes within the <i>ATBF1</i> gene and their effects on economically important production traits in cattle