The Influence of the Wahlund Effect on the Consanguinity Hypothesis: Consequences for Recessive Disease Incidence in a Socially Structured Pakistani Population

Background/Aims: Standard population genetic theory predicts that the relative risk of inheriting recessive disorders between consanguineous and non-consanguineous populations can be manyfold. However, it is rarely considered that consanguineous populations might be composites of socially defined endogamous and genetically differentiated sub-populations. A recent study of a British Pakistani population found evidence to suggest that extended families (biraderi) could contribute significantly to excessive homozygosity over that contributed by consanguinity. This study sets out to illustrate the potential of cryptic population substructure (the Wahlund effect) to contribute to recessive disease incidence in populations with complex social structure. Method: Population parameter estimates were drawn from a recent study of the British Pakistani population along with allele frequency estimates of nine recessive inborn errors of metabolism. The relative contribution of consanguinity and biraderi endogamy to recessive disease incidence was predicted. Results: Population substructure of the magnitude estimated from studies of biraderi endogamy are sufficient to significantly contribute to the incidence of recessive disorders within consanguineous populations. Conclusions: Because non-consanguineous couples have a higher risk of sharing the same recessive mutation in a substructured population relative to a non-substructured population, the health benefits of avoiding consanguinity in these situations is likely to be less pronounced than the standard consanguinity hypothesis predicts. Copyright (C) 2008 S. Karger AG, Basel