Kambiz's review (pointer) to the Humanity's Genes an the Human Condition conference made me aware of Jean-Laurent Casanova's research. His general idea seems to be that heightened susceptibility or death due to infectious disease is in large part a function of inter-individual genetic variation. Among the young this is due to Mendelian genes of large effect, whether it be dominant or recessive (higher frequency among those who are the product of cousin marriage). For the old he suggests that it might be due to QTLs of small effect, just like schizophrenia. To some extent this is a revision to the germ theory of disease; pathogens are necessary, but not sufficient, and operationally they are close to ubiquitous. The general model is laid out in this paper, From monogenic to multifactorial predisposition: the example of infectious diseases:
Human genetics of infectious diseases aims to define the genetic variations accounting for inter-individual variability in the course of human infections. According to the dominant paradigm, monogenic immunodeficiencies (also known as primary immunodeficiencies, PIDs) are rare and confer vulnerability to multiple infectious diseases (one gene, multiple infections) -- that vary in nature and number with the gene affected...whereas common infections are favoured by the polygenic inheritance of multiple susceptibility genes, most of which if not all making an individually modest contribution to the phenotype (one infection, multiple genes)...For Galtonian biostatisticians, infectious diseases are seen in populations and reflect polygenic predisposition. In contrast, for Mendelian physician-scientists, severe infections do occur in individuals and result from monogenic PIDs. X-linked recessive agammaglobulinaemia, probably the first PID to be described as such in the English literature, was discovered in 1952 by Ogden Bruton, in a few American children with multiple nfections...At about the same period, in 1954, Anthony Allison discovered that the sickle cell trait protects against severe forms of P. falciparum malaria in African populations...paving the way for acceptance of the notion of multiple-gene involvement in disease susceptibility....
