Genome-wide association study identifies novel single nucleotide polymorphisms having age-specific effect on...

Area of Science:

• Genetics
• Oncology
• Biochemistry

Background:

• Prostate-specific antigen (PSA) blood tests are crucial for prostate cancer risk assessment and outcome prediction.
• PSA levels naturally increase with age post-puberty.
• While single nucleotide polymorphisms (SNPs) are linked to PSA levels, their interaction with age remains unclear.

Purpose of the Study:

• To investigate the interaction between SNPs and age on prostate-specific antigen (PSA) levels.
• To identify genetic markers with age-specific effects on PSA.

Main Methods:

• Genome-wide association study (GWAS) in a discovery set (2394 men) and validation set (2137 men).
• Linear regression analysis to detect significant SNP × age interactions.
• Expression quantitative trait loci (eQTLs) analysis to assess gene expression impacts.

Main Results:

• Fifteen SNPs across three loci (8p11.22, 8p12, 3q25.31) demonstrated age-specific effects on PSA levels.
• eQTLs analysis revealed that 12 SNPs at the 3q25.31 locus influence the expression of three genes: KCNAB1, SLC33A1, and PLCH1.

Conclusions:

• SNPs exhibit age-specific effects on PSA levels, suggesting a complex interplay.
• These findings open new avenues for researching genetic markers associated with PSA and prostate cancer.