α-Thalassemia has no association with asymptomatic Plasmodium falciparum carriage in three ecological zones of Ghana

α-thalassemia, a hereditary disorder, common in malaria-endemic regions, provides selective advantage by conferring partial protection against severe Plasmodium falciparum malaria. This study investigated the distribution of α-thalassemia genotypes and Plasmodium falciparum carriage among 1401 asymptomatic individuals aged 1–60 years, across Ghana’s coastal, forest, and Sahel savanna ecological zones. DNA was extracted from archived dried blood spots and genotyped for α-thalassemia using multiplex PCR, while malaria was detected through RDT, microscopy, and PCR. Participants from the forest zone had the highest malaria prevalence by PCR (36.5%) compared to those in the Sahel savannah zone (27.6%), and coastal zone (23.5%), p < 0.0001. In the coastal zone, 54.3% (482/887) of participants had the wild type genotype (αα/αα), 41.8% (371/887) were heterozygous carriers (-α/αα), and 3.8% (34/887) were homozygous recessive for α-thalassemia (-α/-α). In the forest zone participants had 66.0% (134/203) wild type, 30.5% (62/203) heterozygous, and 3.5% (7/203) homozygous individuals, while participants in Sahel savannah recorded 62.7% (195/311) wild type, 31.5% (98/311) heterozygous, and 5.8% (18/311) homozygous recessive genotypes. There were higher odds of having asexual parasites (Odds Ratio = 1.23) and an increased odds (Odds Ratio = 1.46) of gametocyte carriage in the homozygous recessive group compared to the wild type, p = 0.447 but there were no statistically significant association observed between α-thalassemia genotype and the presence of asexual P. falciparum stages.