Genome-wide association study and polygenic risk scores of eosinophilia in Taiwan

Abstract

Objectives

Eosinophilia, characterised by elevated eosinophil levels, is associated with various allergic and inflammatory conditions. This study aimed to elucidate the genetic determinants of eosinophil levels by examining polygenic risk scores (PRS) and identifying significant single nucleotide polymorphisms (SNPs).

Methods

We conducted a comprehensive genome-wide association study (GWAS) on eosinophil levels using a large cohort, comprising 221 851 controls (eosinophil levels ≤ 5%) and 11 200 cases (eosinophil levels > 5%) in Taiwan. The analysis included covariates such as age, sex and the first 10 principal components to account for population stratification. Polygenic risk scores were calculated, and their associations with eosinophil levels were evaluated.

Results

The control group exhibited a mean eosinophil level of 47.81 (SD, 21.08) and was composed of 55.32% females and 44.68% males. The case group had a mean eosinophil level of 43.27 (SD, 22.27) and consisted of 38.6% females and 61.4% males. The GWAS identified several SNPs with significant associations, including rs7646596, rs8191981, rs140105250, rs77143352, rs12535759, rs11327184, rs16917546, rs76738175, rs11568075, rs9557175 and rs2801127, with rs7646596 showing the most significant P-value. PRS analysis indicated that individuals with higher polygenic risk scores were significantly more likely to have elevated eosinophil levels.

Conclusion

This study identified several genetic loci significantly associated with eosinophil levels, highlighting the polygenic nature of eosinophilia. The robust associations, particularly with SNP rs7646596, offer valuable insights into the genetic underpinnings of eosinophilia and related conditions.