The IVW estimate for fasting glucose was only nominally significant for both FVC and FEV 1 (p=0.033 and 0.023, respectively), with relatively wide confidence intervals to approach zero, and thus, the estimate should be treated with appropriate caution.
An analogous causal estimate was derived regardless of which IV was removed; however, there were five IVs (FEV 1 model = two outlier single nucleotide polymorphisms (SNPs) , FVC model = four outlier SNPs [two outlier SNPs shared]) for which the estimate was marginally non-significant after exclusion (maximum p=0.11, IVW with multiplicative random effects).
(4b) Likewise, the MR analyses have only a very weak statistical signal (p=.02,.03): 1 this doesn't survive correction for testing two phenotypes (not to mention the implicit tests prioritized by rhog that were discarded based on LCV); 2 the LCV paper proves these tests are susceptible to inflation by genetic correlation; 3 I do not agree that horizontal pleiotropy has been ruled out, a priori it seems almost certain that many heritable traits (BMI, smoking, diet, exercise,....) will causally effect both glucose and lung function, to some extent, and moreover you do show that AMT has near-significant TWAS effects on both smoking and glucose.
Host–viral interactomes suggested proposed pulmonary drug-repurposing candidates may be significant for respiratory virus infection Respiratory viruses are an important contributor to acute, and potentially fatal, declines in lung function.
Reviewers valued the sophisticated approaches applied in this analysis although questioned the authors' statistical interpretations noting that some results were borderline significant.
We are of the view that marginally significant (or null) results can still provide a significant contribution to the field as long as their statistical support is reported appropriately.