Abstract
Human infections with the tissue nematode Onchocerca volvulus show strong interindividual variation in intensity, which cannot be explained by differences in exposure alone. Several lines of evidence suggest a relevant influence of human genetics. In a genome-wide search for genetic determinants of resistance, we studied 196 siblings from 51 families exposed to endemic O. volvulus transmission in the forest zone of Ghana, West Africa. The numbers of worm larvae in the skin (i.e., microfilariae), which are the established measure of O. volvulus infection intensity, were counted in 4 small skin biopsy specimens (i.e., skin snips), and the numbers of palpable subcutaneous worm nodules (i.e., onchocercomata) were assessed. Numbers were corrected for age and exposure and were analyzed for linkage to 377 autosomal microsatellite markers and additional markers in genomic regions of interest. Linkage was detected between the numbers of microfilariae and chromosome 2p21-p14 (maximum multipoint log(10) of odds (LOD) score of 3.80 at marker position D2S2378; empirical P=2.9 x 10(-5)). This finding provides strong evidence that a human genetic factor influences the intensity of O. volvulus infection. The strength of the linkage signal may facilitate the identification of the decisive genetic variants.
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