4.2 Strengths and limitations
Our work has several important strengths. The MR approach can largely
reduce the risk of reverse causality bias and the effect of confounders
by using genetic variation as instrumental variation to analyse the
potential risks of medical abortion. In addition, complementary methods
and MVMR methods were used for pleiotropy and sensitivity analysis,
resulting in reliable conclusions that EA, SB, LNSP, AFB, AFS were
associated with MA. The causal chains of EA-AFB-MA causality were
elaborated through mediated MR. EA was elaborated to impact MA more than
HI by MVMR. Finally, we limited the bias due to population
stratification by using only genetic variants from European populations
in all datasets.
There are several limitations to our study. Firstly, the strength of the
test for multivariate MR was modest, leading to the possibility of false
positives, which could be explained by the insufficient sample size.
Secondly, there were significant heterogeneity in the analyses
addressing the exposure factors: EA, AFS, and AFB, but the conclusions
were plausible because of the consistency of the results from MVMR and
mediated MR. Thirdly, there is a lack of published GWAS articles on
outcome-medical abortion. A bidirectional study is essential if complete
GWAS statistics for medical abortion become available in the future.
Finally, abortion is a worldwide issue, but we only used summary data
from European populations, resulting in data deficits, and this finding
should be validated in other populations in further study.