We appreciate the thoughtful comments and valuable insights provided by other authors regarding our recent publication [1]. Their careful reading and constructive suggestions have offered us an opportunity to clarify potential ambiguities and further elaborate on the relationship between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, alcohol consumption, and risk of ruptured intracranial aneurysms (RIA).

First, we acknowledge and understand the confusion arising from the second sentence in the discussion section. This sentence was intended to emphasize that while our study confirms the independent protective effect of the ALDH2 mutant genotype against RIA (as demonstrated by multivariate logistic regression analysis with an adjusted odds ratio [OR] of 0.49), alcohol consumption could act as a modifier of this relationship, particularly in individuals with the ALDH2*1/*1 genotype, as ALDH2 is essential for the metabolism of ethanol [2]. As elaborated in the Discussion, individuals carrying the ALDH2 mutant genotype (ALDH2*1/*2 or *2/*2) often experience adverse psychophysiological responses to alcohol due to impaired acetaldehyde metabolism, which deters excessive alcohol intake [3,4]. This reduced alcohol consumption may indirectly reinforce the protective effect of ALDH2 mutation. In contrast, those with the ALDH2*1/*1 genotype are more likely to consume alcohol, which could elevate their risk of RIA. This constitutes a reverse inference based on the results of our study. Thus, the interaction between the ALDH2 genotype and alcohol consumption does not contradict the independent protective role of the ALDH2 mutation but rather adds nuance to our understanding of how lifestyle factors intersect with genetic predispositions.

Second, we fully agree with the suggestion that incorporating an interaction term between ALDH2 rs671 polymorphism and alcohol consumption, as well as conducting stratified analyses by genotype to examine the effects of alcohol, would provide deeper insights. The lack of data on the duration of alcohol consumption was a notable limitation. Additionally, the limited number of heavy drinkers among ALDH2 mutant carriers (as reflected in the missing OR for the heavy drinking stratum in Table 5) constrained our ability to perform more detailed subgroup analyses. We are planning follow-up studies to address these limitations, and hope to share these results in the future.

Finally, we thank the other authors for their interest in our work and welcome the publication of their research findings. Academic progress has thrived from diverse perspectives and rigorous debates, and we are eager to compare our results with theirs to advance our collective understanding of the genetic and lifestyle determinants of RIA risk.