Angiotensin-Converting Enzyme (ACE) and ABO Polymorphisms in Schizophrenia: Risk Factors and Age-of-Onset Stratification in an Algerian Population

North African populations remain underrepresented in genomic studies of schizophrenia. This case-control study evaluated the ACE I/D polymorphism and ABO blood group phenotypes as candidate risk factors in an Algerian cohort, with stratification by age of onset. This case-control study recruited 166 individuals from the Tlemcen region, evenly split between 83 clinically diagnosed schizophrenia patients and 83 healthy controls. Patients were stratified by age of onset to isolate early-onset (young adults, 20–35 years) and late-onset (older subjects, 45–75 years) subgroups. Risk associations were calculated using logistic regression to yield adjusted odds ratios (OR) after controlling for age, sex, tobacco smoking and cannabis exposure status. Across the broader cohort, the ACE II genotype was significantly associated with a reduced risk of schizophrenia compared to the DD genotype (OR = 0.13, 95% CI: 0.03–0.61, P = 0.003). Stratified analysis showed nominal significance in early-onset (P = 0.039) but not late-onset patients (P = 0.81); however, overlapping 95% CIs (0.03–0.91 vs. 0.14–4.68) and the absence of a formal interaction test mean these data do not confirm an age-dependent ACE effect. In early-onset patients, ABO B/AB phenotype was nominally associated with risk. The ‘B’ allele emerged as a potential age-specific risk factor for early-onset cases (OR = 8.66, 95% CI: 0.94–79.96, P = 0.041); however, it does not survive Bonferroni correction and should be regarded as an uncorrected, exploratory signal. The protective nature of the ACE ‘I’ allele and the early-onset susceptibility tied to the ABO ‘B’ allele provide exploratory signals requiring further validation in larger cohorts. Neither finding withstands Bonferroni correction for multiple testing or independent replication; given the limited subgroup sample sizes, these exploratory findings warrant cautious interpretation. These findings provide a preliminary epidemiological baseline for psychiatric genetics in North Africa.