Paper detail

The Expected Linkage Disequilibrium in Finite Populations Revisited

The expected level of linkage disequilibrium (LD) in a finite ideal population at equilibrium is of relevance for many applications in population and quantitative genetics. Several recursion formulae have been proposed during the last decades, whose derivations mostly contain heuristic parts and therefore remain mathematically questionable. We propose a more justifiable approach, including an alternative recursion formula for the expected LD. Since the exact formula depends on the distribution of allele frequencies in a very complicated manner, we suggest an approximate solution and analyze its validity extensively in a simulation study. Compared to the widely used formula of Sved, the proposed formula performs better for all parameter constellations considered. We then analyze the expected LD at equilibrium using the theory on discrete-time Markov chains based on the linear recursion formula, with equilibrium being defined as the steady-state of the chain, which finally leads to a formula for the effective population size N_e. An additional analysis considers the effect of non-exactness of a recursion formula on the steady-state, demonstrating that the resulting error in expected LD can be substantial. In an application to the HapMap data of two human populations we illustrate the dependency of the N_e-estimate on the distribution of minor allele frequencies (MAFs), showing that the estimated N_e can vary by up to 30% when a uniform instead of a skewed distribution of MAFs is taken as a basis to select SNPs for the analyses. Our analyses provide new insights into the mathematical complexity of the problem studied.