Effects of worldwide population subdivision on ALDH2 linkage disequilibrium

The effect of human population subdivision on linkage disequilibrium has previously been studied for unlinked genes. However, no study has focused on closely linked polymorphisms or formally partitioned linkage disequilibrium within and among worldwide populations. With an emphasis on population subdivision, the goal of this paper is to investigate the causes of linkage disequilibrium in ALDH2, the gene that encodes aldehyde dehydrogenase 2. Haplotypes for 756 people from 17 populations across five continents were estimated by maximum-likelihood from genotypes at six closely linked ALDH2 nucleotide substitutions. Linkage disequilibrium was partitioned into three components: within populations, among populations within continents, and among continents. It was found that population subdivision among continents had a larger and more disparate effect on linkage disequilibrium than subdivision among local populations. Further, linkage disequilibrium did not increase with population divergence as predicted by a simple model. Rather, the patterns of linkage disequilibrium were complicated because of the interplay of a near absence of recombination, the linkage disequilibrium that existed prior to the divergence of modern humans, subsequent mutation, population subdivision, random genetic drift, and perhaps natural selection. These results suggest that simple models may not well predict patterns of linkage disequilibrium in human populations.