A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic...

Area of Science:

• Genetics and Genomics
• Urology
• Molecular Biology

Background:

• Benign prostatic hyperplasia (BPH) is a common urinary disorder with a known genetic component, but specific genes and mechanisms remain unclear.
• Understanding the genetic underpinnings of BPH is crucial for developing targeted therapies and preventative strategies.

Purpose of the Study:

• To identify specific genes and biological mechanisms contributing to the genetic susceptibility of benign prostatic hyperplasia (BPH).
• To pinpoint the key genetic risk factor for BPH using large-scale genetic datasets and advanced bioinformatics analyses.

Main Methods:

• Utilized transcriptome-wide association studies (TWAS) on the FinnGen R10 dataset (177,901 individuals) and GTEx v8 EQTLs.
• Employed methods including FUSION, MAGMA, Mendelian randomization (MR), SMR, colocalization, and FOCUS for gene identification and validation.
• Verified gene expression changes using Gene Expression Omnibus (GEO) data and explored functional roles with GeneMANIA.

Main Results:

• Cross-tissue TWAS identified 28 genes associated with BPH susceptibility, refined to eight by single-tissue TWAS and MAGMA.
• Integrated MR, SMR, FOCUS, and colocalization analyses pinpointed INO80B as the key susceptibility gene for BPH.
• INO80B differential expression was confirmed via GEO, suggesting its role in regulating cell cycle-related gene expression to prevent prostatic cell overproliferation.

Conclusions:

• The study identified INO80B as a novel genetic risk factor for benign prostatic hyperplasia (BPH), linking its expression to disease susceptibility.
• INO80B's potential role in regulating cell cycle genes offers a new perspective on the genetic basis of BPH.
• Further functional studies are warranted to fully elucidate the biological activity and therapeutic potential of INO80B in BPH.