No abstract

Asthma is a common chronic respiratory disease. In the past 10 years, genome-wide association study (GWAS) has been widely used to identify the common asthma genetic variants. Importantly, these publicly available asthma GWAS datasets provide important data support to investigate the causal association of kinds of risk factors with asthma by a Mendelian randomization (MR) design. It is known that socioeconomic status is associated with asthma. However, it remains unclear about the causal association between socioeconomic status and asthma. Here, we selected 162 independent educational attainment genetic variants as the potential instruments to evaluate the causal association between educational attainment and asthma using large-scale GWAS datasets of educational attainment (n = 405,072) and asthma (n = 30,810). We conducted a pleiotropy analysis using the MR-Egger intercept test and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. We performed an MR analysis using inverse-variance weighted, weighted median, MR-Egger, and MR-PRESSO. The main analysis method inverse-variance weighted indicated that each 1 standard deviation increase in educational attainment (3.6 years) could reduce 35% asthma risk [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51–0.85, P = 0.001]. Importantly, evidence from other MR methods further supported this finding, including weighted median (OR = 0.55, 95% CI 0.38–0.80, P = 0.001), MR-Egger (OR = 0.48, 95% CI 0.16–1.46, P = 0.198), and MR-PRESSO (OR = 0.65, 95% CI 0.51–0.85, P = 0.0015). Meanwhile, we provide evidence to support that educational attainment protects against asthma risk dependently on cognitive performance using multivariable MR analysis. In summary, we highlight the protective role of educational attainment against asthma. Our findings may have public health applications and deserve further investigation.

Photorhabdus luminescens, a Gram-negative bacterium, secretes a protein toxin (PL toxin) that is toxic to insects. In this study, the effects of the PL toxin on large receptor-free unilamellar phospholipid vesicles (LUVs) of Manduca sexta and on brush border membrane vesicles (BBMVs) of M. sexta and Tenebrio molitor were examined. Cry1Ac served as a positive control in our experiments due to its known channel-forming activity on M. sexta. Voltage clamping assays with dissected midguts of M. sexta and T. molitor clearly showed that both Cry1Ac and PL toxin caused channel formation in the midguts, although channel formation was not detected for T. molitor midguts under Cry1Ac and it was less sensitive to PL toxin than to Cry1Ac for M. sexta midguts. Calcein release experiments showed that both toxins made LUVs (unilamellar lipid vesicles) permeable, and at some concentrations of the toxins such permeabilizing effects were pH-dependent. The lowest concentrations of PL toxin were more than 600-fold and 24-fold lower to induce BBMV permeability of T. molitor and M. sexta than those to induce calcein release from LUVs of M. sexta. These further support that PL toxin is responsible for channel formation in the larvae midguts. The lower concentration to induce permeability in BBMV than in LUV is, probably, attributable to that BBMV has PL toxin receptors that facilitate the toxin to induce permeabilization. Furthermore, our results indicate that the effects of PL toxin on BBMV permeability of M. sexta were not significantly influenced by Gal Nac, but those of Cry1Ac were. This implies that PL toxin and Cry1Ac might use different molecular binding sites in BBMV to cause channel formation.