Decreased FAM13B Expression Increases Atrial Fibrillation Susceptibility by Regulating Sodium Current and Calcium Handling

Tchou, Gregory; Ponce-Balbuena, Daniela; Liu, Nana; Gore-Panter, Shamone R.; Hsu, Jeffrey; Liu, Fang; Opoku, Emmanuel; Brubaker, Gregory; Schumacher, Sarah M.; Moravec, Christine S.; Barnard, John; Wagoner, David R. Van; Chung, Mina K.; Smith, Jonathan

doi:10.1016/j.jacbts.2023.05.009

Cited by 4 publications

(1 citation statement)

References 48 publications

(71 reference statements)

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“…These include studies on the top locus on chromosome 4q25 near PITX2, [10][11][12] which is associated with development of pulmonary veins, and on a locus on chromosome 5, associated with functional changes in FAM13B. 13 However, identification of putative function for these loci has yet to achieve clinical applicability, which will be critical if these genomic findings are to be translated to the bedside. This highlights the need for further in-depth research on additional AF-associated genes and insights to translate this knowledge into AF prevention or treatment.…”

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Connecting the Dots From GWAS to Function in Atrial Fibrillation for ZFHX3

Wass

Smith

Chung

2023

Circulation Research

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enetics significantly influence susceptibility to atrial fibrillation (AF). Individuals with first-degree relatives under 60 years old with AF have ≈5× higher risk 1 with heritability estimated at 22%. 2 Genetic burden can be divided into 2 main categories: rare variants with strong effects, often due to loss of function mutations, and common variants (most often single nucleotide polymorphisms, SNPs) that can additively increase AF susceptibility. Common AF-associated variants are identified by genome-wide association studies (GWAS). The first published GWAS of AF in 2007 reported SNPs on 4q25 near PITX2. 1 In 2010 variants near ZHFX3 (zinc finger homeobox 3) were identified. 2 With increasing cohort size, over 100 AF risk loci have now been identified. 3 However, despite advancements in genomics, our understanding of the pathological mechanisms of AF remains nebulous. Article, see p 313Polygenic risk scores for AF, using tens to millions of common variants, estimate that individuals in the top percentile have 4.6-fold increased risk of AF. 4 Exome sequencing in ≈43 000 UK Biobank subjects revealed that common variants explain >20-fold more of the AF variance than the rare variants. 5 Thus, GWAS identify the loci responsible for most of the population-attributable genetic risk for AF. GWAS loci, using Manhattan plots, display variants at each locus with ascending significance by P value. Most of these variants are a result of linkage disequilibrium (LD), implying they are often inherited together from ancestral chromosomes. However, discovering these loci is just the first step in the arduous tasks of identifying the responsible gene, variant(s), and mechanism for disease association.

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confidence: 99%

Connecting the Dots From GWAS to Function in Atrial Fibrillation for ZFHX3

Wass

Smith

Chung

2023

Circulation Research

Self Cite

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Atrial fibrillation variant-to-gene prioritization through cross-ancestry eQTL and single-nucleus multiomic analyses

Leblanc,

Jin,

Kang

et al. 2024

iScience

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The impact of chronic pain on brain gene expression

Collier,

Seah,

Hicks

et al. 2024

Preprint

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Background: Chronic pain affects one fifth of American adults, contributing significant public health burden. Chronic pain mechanisms can be further understood through investigating brain gene expression. Methods: We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, and with chronic pain genetic risk in four brain regions (dACC, DLPFC, MeA, BLA) and imputed cell type expression data from 304 postmortem donors. We compared findings across traits and with independent transcriptomics resources, and performed gene-set enrichment. Results: We identified two chronic pain DEGs: B4GALT and VEGFB in bulk dACC. We found over 2000 (primarily BLA microglia) chronic pain cell type DEGs. Findings were enriched for mouse microglia pain genes, and for hypoxia and immune response. Cross-trait DEG overlap was minimal. Conclusions: Chronic pain-associated gene expression is heterogeneous across cell type, largely distinct from that in pain-related traits, and shows BLA microglia are a key cell type.

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Decreased FAM13B Expression Increases Atrial Fibrillation Susceptibility by Regulating Sodium Current and Calcium Handling

Cited by 4 publications

References 48 publications

Connecting the Dots From GWAS to Function in Atrial Fibrillation for ZFHX3

Connecting the Dots From GWAS to Function in Atrial Fibrillation for ZFHX3

Atrial fibrillation variant-to-gene prioritization through cross-ancestry eQTL and single-nucleus multiomic analyses

The impact of chronic pain on brain gene expression

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