Decreased FAM13B expression increases atrial fibrillation susceptibility by regulating sodium current and calcium handling

Objectives: To determine the causal genetic variant and gene and the mechanism for the atrial fibrillation (AF) genome wide association study (GWAS) locus on chromosome 5q31.
Background: FAM13B expression is strongly associated with the lead AF GWAS variant at 5q31.  However, the regulatory variant controlling FAM13B expression and the mechanism by which FAM13B impacts AF susceptibility are not known.
Methods: Bioinformatics, reporter gene transfections, gel shifts, and gene editing were used to identify the variant regulating FAM13B expression. RNAseq after FAM13B knockdown in stem cell-derived cardiomyocytes (iCMs) identified downstream processes. Patch clamp and calcium transient assays were used to assess downstream mechanisms. Fam13b knockout (KO) mice were studied for heart structural and functional changes, and pacing-induced arrhythmia.
Results: rs17171731 was identified as the regulatory variant controlling FAM13B expression, with decreased enhancer activity of the risk allele...., , Excel and proprietary software: Labscribe ECG Analysis software (iWorx RA834)., # Decreased FAM13B expression increases atrial fibrillation susceptibility by regulating sodium current and calcium handling

Data repositories: Left atrial appendage variance normalized RNAseq gene expression levels for each subject are available in the GEO database, accession number GSE69890.
Human LAA eQTL data can be obtained on our web browser: .\
Custom scripts for eQTL analyses are available here: .\
RNAseq data from iCell cardiomyocyte FAM13B siRNA vs. scrambled siRNA treatment are available in the GEO database, accession number GSE221262.
Data for graphs: Excel file with worksheets for different figures

## Description of the data and file structure

The Excel file has different worksheets for different figures.
The zip file has mouse electophysiology folders for 4 types of mice, WT, FAM13B KO of both males and females.
These files consist of Excel files, ascii and txt files that can be opened in Microsoft Notepad or other text editors.

## Sharing/Access information

Links to ...