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Case-control studies have indicated that genes for the major histocompatibility complex influence the presentation and outcome of severe Plasmodium falciparum disease. To assess the role of genetic factors in mild malaria, an analysis was conducted in 217 pairs of Gambian twins (mean age, 5.3 years) concordant for this phenotype. The twins were monitored weekly during three rainy seasons (1991-93) for fever and P. falciparum infection. This surveillance produced a total of 40 pairs of twins who were concordant for clinical malaria; none had severe disease. In the 22 of these 40 families with complete information, 11 had two shared alleles (expected value, 5.5), 10 shared one allele (expected value, 11.0), and 1 shared no allele (expected value, 5.5). If a locus is genetically linked to disease, affected siblings will share a higher than expected number of alleles identical by descent at that locus. Sharing of major histocompatibility complex alleles was not increased among the 13 pairs of dizygous twins who were discordant for malaria. These findings confirm the importance of genetic factors to the risk of uncomplicated malaria

Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs