The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

“…Also, in our large cohort, we showed no causal association of eosinophils with pulmonary intermediate traits (FEV 1 and FEV 1 /FVC) as determinants of pulmonary diseases pathophysiology. Our results were inconsistent with a study from the United Kingdom, which indicated significant causal associations between eosinophils and asthma, and provided evidence that eosinophils are key effector cells in the pathogenesis of asthma (Astle et al, 2016). The observed causal association in that study may be explained by a larger sample size and stronger instrumental variable (Astle et al, 2016).…”

“…Our results were inconsistent with a study from the United Kingdom, which indicated significant causal associations between eosinophils and asthma, and provided evidence that eosinophils are key effector cells in the pathogenesis of asthma (Astle et al, 2016). The observed causal association in that study may be explained by a larger sample size and stronger instrumental variable (Astle et al, 2016). Since patients with pulmonary diseases can be clinically or physiologically stratified into several subgroups (Fahy, 2015), the lack of causal associations in our study might be due to biases by subgroup stratification or possibly insufficient power to identify a relatively small causal effect of eosinophil on pulmonary outcomes in our database.…”

“…We found 67 genetic correlations passing Bonferroni adjusted significance (p < 10 −4 ), which are consistent with well-known associations between the blood cell traits themselves and the disease. For example, prior studies have demonstrated a strong association of asthma with eosinophil indices, 4 consistent with our analyses, which show that PGSs for eosinophil counts (EO#) and eosinophil percentages (EO%) were correlated with the asthma PGS. The strongest genetic correlation was between schizophrenia and WBC#, consistent with previous studies of the trait and schizophrenia risk.…”

“…We next evaluated the relationship between the pQTL minor allele frequency, its absolute effect size, the absolute variability of the associated protein, and the fraction of such variability explained by the pQTL. Consistent with previous studies 21,27,54–56 , we observed a significant negative correlation between the minor allele frequency (MAF) and the absolute effect size of the SNPs (Spearman’s rho = −0.30, p-value = 1e-03). In addition, we observed a mild positive correlation between the MAF and the variability explained by the pQTLs (Spearman’s rho = 0.25, p-value = 7e-03), as well as a strong positive correlation between the absolute effect size and the explained variability (Spearman’s rho = 0.57, p-value < 2.2e-16).…”