Association between Maternal Hypertension and Cleft Lip and Palate: A Mendelian Randomization Study

There is still no consensus on the etiology and risk factors of cleft lip and palate, and the causal relationship between maternal hypertension and cleft lip and palate remains uncertain.

We used two-sample Mendelian Randomization (MR) to investigate the causal effect of maternal hypertension on cleft lip and palate.

The MR study was performed using the statistics from the Genome-Wide Association Studies (GWAS) of maternal hypertension and cleft lip and palate. Using 25 Single-Nucleotide Polymorphisms (SNPs) robustly associated with maternal hypertension as instrumental variables, we employed several MR approaches, including Inverse Variance Weighted (IVW), weighted median, simple mode, MR-Egger, and weighted mode. Heterogeneity and pleiotropy tests were also conducted.

The causal relationship between maternal hypertension and cleft lip and palate (CL/P) was identified using IVW (OR = 3.603, 95% CI = 1.184-10.964, p = 0.024). Additionally, a causal effect of maternal hypertension on cleft lip (CL) risk was identified using IVW (OR = 5.968, 95% CI = 1.023-34.819, p = 0.047). However, no significant association between maternal hypertension and Cleft Palate Only (CPO) was observed across all MR methods.

The MR analysis indicated that maternal hypertension is causally associated with the risk of CL/P and CL.