Whole-blood transcriptomics in a Japanese population cohort: physiological and methodological insights

Area of Science:

• Genomics
• Transcriptomics
• Human Physiology

Background:

• Whole blood transcriptomics offers insights into human physiology but lacks systematic analysis in healthy cohorts.
• Uncertainty exists regarding age and sex influences on gene expression and the necessity of globin mRNA removal.

Purpose of the Study:

• To establish a foundational whole-blood gene-expression reference dataset for the Japanese population.
• To investigate the impact of age, sex, and immune cell composition on gene expression profiles.
• To provide methodological guidance on handling globin transcripts in RNA sequencing.

Main Methods:

• Large-scale whole-blood RNA sequencing (RNA-seq) from 576 healthy Japanese participants.
• Retained globin transcripts initially, followed by in silico removal for analysis.
• Analysis focused on identifying age- and sex-dependent signatures and immune cell composition drivers.

Main Results:

• Detected rare Hereditary Persistence of Fetal Hemoglobin (HPFH) cases.
• Identified immune cell composition, specifically the neutrophil-to-lymphocyte ratio, as a major driver of gene expression variance.
• Uncovered extensive age- and sex-dependent gene expression signatures, including pregnancy-associated NRF2 activation.

Conclusions:

• The study establishes standardized, stratified baseline profiles for the Japanese population.
• Provides practical guidance on globin transcript handling in whole-blood RNA-seq.
• The dataset will inform population-aware blood transcriptomics and enhance understanding of human physiology.