Genome-Wide Association Study to Identify Novel Genetic Variants Associated With Primary Budd-Chiari Syndrome

Area of Science:

• Genetics
• Vascular Biology
• Hepatic Disorders

Background:

• Primary Budd-Chiari syndrome (BCS) is a rare hepatic vascular disorder causing hepatic venous outflow obstruction.
• Geographic variations and prothrombotic profiles suggest a genetic basis for BCS.
• Identifying genetic predispositions is crucial for understanding BCS etiology.

Purpose of the Study:

• To identify genetic variants associated with primary BCS using genome-wide association study (GWAS).
• To characterize the biological pathways implicated by these genetic variants.
• To explore potential genetic risk factors beyond classical thrombophilia genes.

Main Methods:

• A case-control study involving 310 primary BCS patients and 312 healthy controls.
• Whole-blood DNA genotyping using high-density single-nucleotide polymorphism (SNP) arrays.
• Bioinformatic analyses including gene ontology, pathway, and tissue-expression assessments.

Main Results:

• Analysis of 778,783 SNPs revealed 340 lead SNPs associated with primary BCS.
• Top SNPs were located in noncoding and regulatory regions, not canonical hypercoagulable genes.
• Functional enrichment analysis implicated extracellular matrix remodeling, cell-cell junctions, focal adhesion, and vasoconstriction pathways.

Conclusions:

• This GWAS identified novel germline loci in primary BCS, primarily in noncoding/regulatory regions.
• The findings highlight the roles of extracellular matrix remodeling, vascular tone, and cell adhesion in BCS.
• Further functional studies are recommended for refining genetic risk stratification in primary BCS.