Effective Population Size of Korean Populations

Recently, new methods have been developed for estimating the current and recent changes in effective population sizes. Based on the methods, the effective population sizes of Korean populations were estimated using data from the Korean Association Resource (KARE) project. The overall changes in the population sizes of the total populations were similar to CHB (Han Chinese in Beijing, China) and JPT (Japanese in Tokyo, Japan) of the HapMap project. There were no differences in past changes in population sizes with a comparison between an urban area and a rural area. Age-dependent current and recent effective population sizes represent the modern history of Korean populations, including the effects of World War II, the Korean War, and urbanization. The oldest age group showed that the population growth of Koreans had already been substantial at least since the end of the 19th century.

An Alternative Way of Constructing Ancestral Graphs Using Marker Allele Ages from Population Linkage Disequilibrium Information

An alternative way of constructing ancestral graphs, which is different from the coalescent-based approach, is proposed using population linkage disequilibrium (LD) data. The main difference from the existing method is the construction of the ancestral graphs based on variants instead of individual sequences. Therefore, the key of the proposed method is to use the order of allele ages in the graphs. Distinct from the previous age-estimation methods, allele ages are estimated from full haplotype information by examining the number of generations from the initial complete LD to the current decayed state for each two variants depending on the direction of LD decay between variants. Using a simple algorithmic procedure, an ancestral graph can be derived from the expected allele ages and current LD decay status. This method is different in many ways from previous methods, and, with further improvement, it might be a good replacement for the current approaches.

Controlling Linkage Disequilibrium in Association Tests: Revisiting APOE Association in Alzheimer's Disease

The allele frequencies of markers as well as linkage disequilibrium (LD) can be changed in cases due to the LD between markers and the disease allele, exhibiting spurious associations of markers. To identify the true association, classical statistical tests for dealing with confounders have been applied to draw a conclusion as to whether the association of variants comes from LD with the known disease allele. However, a more direct test considering LD using estimated haplotype frequencies may be more efficient. The null hypothesis is that the different allele frequencies of a variant between cases and controls come solely from the increased disease allele frequency and the LD relationship with the disease allele. The haplotype frequencies of controls are estimated using the expectation maximization (EM) algorithm from the genotype data. The estimated frequencies are applied to calculate the expected haplotype frequencies in cases corresponding to the increase or decrease of the causative or protective alleles. The suggested method was applied to previously published data, and several APOE variants showed association with Alzheimer's disease independent from the APOE epsilon4 variant, rs429358, regardless of LD showing significant simulated p-values. The test results support the possibility that there may be more than one common disease variant in a locus.