Who are the Okinawans? Ancestry, genome diversity, and implications for the genetic study of human longevity from a geographically isolated population

Abstract

Isolated populations have advantages for genetic studies of longevity from decreased haplotype diversity and long-range linkage disequilibrium. This permits smaller sample sizes without loss of power, among other utilities. Little is known about the genome of the Okinawans, a potential population isolate, recognized for longevity. Therefore, we assessed genetic diversity, structure, and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese, and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human Mapping 500K array. Principal component analysis, haplotype coverage, and linkage disequilibrium decay revealed a distinct Okinawan genome-more homogeneity, less haplotype diversity, and longer range linkage disequilibrium. Population structure and admixture analyses utilizing 52 global reference populations from the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered almost exclusively with East Asians. Sibling relative risk (λs) analysis revealed that siblings of Okinawan centenarians have 3.11 times (females) and 3.77 times (males) more likelihood of centenarianism. These findings suggest that Okinawans are genetically distinct and share several characteristics of a population isolate, which are prone to develop extreme phenotypes (eg, longevity) from genetic drift, natural selection, and population bottlenecks. These data support further exploration of genetic influence on longevity in the Okinawans.

Keywords: Ancestry; Genome diversity; HapMap.; Longevity; Okinawa.

Figure 1.

Allele frequency distribution in the Okinawan population and the four HapMap populations. Comparison of the distribution of minor allele frequency in the seven allele frequency bins between the Okinawan population and the four HapMap populations (JPT: Japanese, CHB: Han Chinese, CEU: Caucasian from Utah, YRI: Yoruban from Nigeria). The plot shows that the frequency of nonpolymorphic single-nucleotide polymorphisms (SNPs) in the Okinawans, Chinese, and Japanese (~20%) is higher compared with the Caucasians and Yoruban. For common SNPs, there was no difference in minor allele frequency between the Okinawan and HapMap samples. This shows that Asians have less diverse genomes with higher proportion of nonpolymorphic SNPs compared with the Caucasians and the Yoruban. The color version of this figure is available online.

Figure 2.

Principal component analysis (PCA) plots for the Okinawan population and the four HapMap populations. (A) PCA showing projection of the four HapMap populations and Okinawan samples on the top three principal components (Okinawans in green, Japanese in blue, Chinese in red, Caucasians in yellow, and Yoruban in black); 53.1%, 5.6%, and 2.8% of the variance were explained by PC1, PC2, and PC3, respectively. The Okinawans clustered closer to Japanese and Chinese and further away from the Caucasian and the Yoruban. (B) PCA results show the projection of the Okinawan, Japanese, and Chinese samples on the top three principal components (middle-aged Okinawans in green, Okinawan centenarians in gray, Japanese in blue, and Chinese in red); 63%, 0.7%, and 0.3% of the variance were explained by PC1, PC2, and PC3, respectively. The plot suggests: (i) the Okinawans are genetically homogenous and cluster distinctly from the Chinese and the Japanese, (ii) Okinawan centenarians tend to cluster together suggesting some shared genetic loci for longevity. The color version of this figure is available online.

Figure 3.

Linkage disequilibrium (LD) decay over distance in the Okinawan and the four HapMap populations. This plot shows the LD decay over distance in the Okinawans is longer compared with the four HapMap populations (JPT: Japanese, CHB: Han Chinese, CEU: Caucasian from Utah, YRI: Yoruban from Nigeria). This suggests that the Okinawans are a population isolate with less genetic diversity and long stretches of LD. The color version of this figure is available online.

Figure 4.

Summary plot of individual admixture proportions. (A) Summary plot of individual admixture proportions. These data demonstrate Okinawan ancestry proportions on a global scale from comparisons with 944 Human Genome Diversity Cell Line Panel (HGDP) participants, grouped into seven main global regions/continents (Africa, Europe, Middle East, Central/South Asia, Americas, and Oceania). From the admixture proportions plot, the Okinawans cluster primarily with East Asians and very little contribution (<1% individual ancestry estimates) from the remaining global regions. (B) Summary plot of individual admixture proportions. These data demonstrate the results of individual admixture proportions estimated from 680 Ancestry Informative Markers (AIMs), which are polymorphisms that exhibit substantially different frequencies between populations from different geographical regions and can be used to estimate the ancestry of an individual. Each individual is represented by a single vertical line broken into two colored segments, with lengths proportional to each of the two inferred clusters. Pink-colored shade indicates the Han Chinese ancestry proportion, and purple-colored shade indicates the Japanese ancestry proportion. The predefined populations Japanese, Han Chinese, and Okinawans are presented on the abscissa and the ordinate indicates the admixture proportion. On average, the Okinawans were found to share 80.8% (±11.2 SD) admixture with Japanese and 19.2% (±11.2 SD) admixture with Chinese suggesting that the Okinawans and the Japanese share substantial common ancestry. The color version of this figure is available online.