Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

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Abstract. In this paper we propose a solution to the similarity measuring for heterogenous data. The key idea is to consider the similarity of a given attribute-value pair as the probability of picking randomly a value pair that is less similar than or equally similar in terms of order relations defined appropriately for data types. Similarities of attribute value pairs are then integrated into similarities between data objects using a statistical method. Applying our method in combination with distance-based clustering to real data shows the merit of our proposed method.

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