Understanding the interplay of Caesarean delivery and genetic influences on intelligence and anxiety traits in offspring findings from genome-wide association studies.

Background: Recent research suggests that genetic factors linked to Caesarean delivery may influence variations in children's intelligence and anxiety traits. This review synthesizes findings from genome-wide association studies (GWAS) to examine these associations, clarifying that it does not establish causation. Methods: This review systematically aggregated findings from GWAS studying the impact of Caesarean delivery on intelligence and anxiety traits. A thorough literature search was performed in key scientific databases like PubMed and Scopus, using various keywords related to delivery methods, cognitive traits, and psychological outcomes from 2005, when the first GWAS was published, through December 1, 2024. The inclusion criteria focused on original research articles published in English, excluding studies involving non-human subjects or without empirical data. The quality of the studies was assessed using a modified STROBE checklist adapted for GWAS. Results: Five GWAS identified 36 significant genetic loci associated with intelligence and anxiety traits in offspring related to Caesarean delivery. In terms of verbal intelligence, four alleles were found to be significantly linked to decreased scores, with allele rs1276529-G associated with a mean reduction of -2.04 units (p = 1E-6). Conversely, allele rs705670-G correlated with an increase in performance intelligence scores, resulting in a mean elevation of 2.3 units (p = 3E-7). Several alleles exhibited a negative correlation with overall intelligence, particularly rs17800861-A, which was associated with a mean decrease of 3.32 units (p = 7E-7). Significant risk alleles for anxiety were also identified, including rs62389045-C, linked to a 117 % increase in the risk of anxiety symptoms (p = 4E-8). Furthermore, in the context of self-injury, 17 risk alleles were identified, with allele rs117077436-C demonstrating an odds ratio of 11.34 (p = 3E-9). Conclusion: This study highlights multiple genetic loci associated with verbal performance, overall intelligence, and susceptibility to anxiety, revealing significant variations in offspring delivered via Caesarean section. While certain alleles are linked to increased risks of anxiety and self-injurious behavior, the results underscore the presence of genetic predispositions influencing cognitive and psychological outcomes. It is essential to emphasize that GWAS findings indicate associations rather than causal relationships. Further exploration into the biological mechanisms and environmental interactions that underlie these complex traits is warranted.