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.