Genetic differences between Japanese individuals can be largely divided into one of two genetic groups: “mainland” and “Ryukyuan” (Okinawan), according to researchers at the semi-governmental Riken research institute.
Their theory suggests that variances in physical traits, such as hair thickness and whether earwax is dry or wet, are the result of differences in single base pairs in the human genetic code, or single nucleotide polymorphisms (SNPs).
The genome of an average human is made up of around 3.2 billion base pairs, and one in 1,200 to 1,500 pairs shows SNPs. The study examined 140,000 SNPs from each of 7,000 Japanese, finding that the differences could be assigned to two regional groups, with striking differences found for traits like hair thickness.
Almost all those surveyed from the Tohoku, Tokai and Hokuriku areas were in the mainland group, with those in Kyushu showing a higher incidence of traits from the Ryukyu group.
Researcher Naoyuki Kamatani said: “When examining an illness outbreak or drug efficiency from a genetic standpoint, these regional differences must be taken into consideration. Also, if we combine our data with that from other Asian countries, perhaps we could explain the movements of different racial groups.”
(Mainichi Japan) September 26, 2008
Our present study has clearly shown, on the basis of analysis of genome-wide SNP genotypes that most Japanese individuals fall into two main clusters: the Hondo cluster and the Ryukyu cluster. Our results also show that local regions in Honshu Island (the largest island of Japan) are still genetically differentiated, even though human migration within Japan has become rather frequent in the past 100 years or so. Our finding that the individuals from Tohoku were less related to Han-Chinese individuals than were the individuals from Kinki and Kyushu suggests that the individuals in Tohoku were less affected by immigrants from the Asian continent than were the individuals in Kinki. The immigrants who came to Japan from the Asian continent through the Korean Peninsula may have entered Japan from northern Kyushu, the Japan Sea side of Kinki or Chugoku. Our finding that the individuals from the western areas in the Hondo cluster had smaller values of Eigenvector 2 than did those in the eastern areas may be because the northeast areas of Japan, such as Tohoku, are distant from the main contact point to the Asian continent. On the other hand, the individuals from Kanto-Koshinetsu and Hokkaido were broadly distributed in the PCA plots, which is not consistent with the east-west trend of genetic differentiation. The broad distribution of the individuals from Kanto-Koshinetsu may be due to recent migrations from various areas of Japan into the Kanto area. The Kanto area includes large cities, such as Tokyo and Yokohama, and recent migrations from various areas of Japan into the Kanto area may have obscured ancient genetic differentiation in the Kanto area. The individuals in Hokkaido are similar to those in the Kanto-Koshinetsu area, even though Hokkaido is located at the north end of Japan. This is probably because most of the people living in Hokkaido are descendents of people who moved from Honshu. The current population of Ainu (an ethnic group indigenous to Hokkaido) was estimated to be about 25,000, and this is ∼0.5% of the whole population in Hokkaido.
Previous studies showed genetic affinities between the Ainu and Ryukyu peoples,21 and 33 who live in the north and south ends of Japan, respectively, and who are thought to be descendents of the Jomon people. These observations are consistent with the “dual-origin hypothesis”,22 which states that the ancestral Japanese populations were brought by two major migration events.17, 19, 20 and 21 Archeological studies have suggested that the Jomon period (the Japanese Neolithic age) started about 16,000 years ago and ended about 3000 years ago, when the Yayoi period, a rice-farming and metal-using age, started. In the Yayoi period, immigrants from the Asian continent had moved to western Japan via Korea or China and expelled or mixed with the Jomon people. Our observations of the two main clusters and genetic differentiation among geographic regions are not discordant with the dual-origin hypothesis, although most of the Hokkaido individuals in this study are probably different from the indigenous Ainu people. Most of the people living in Okinawa Island are probably derived from the Jomon people, whereas most of the people living in Hondo are probably derived from the Yayoi people or are a mixture of the Yayoi and Jomon peoples. Individuals in Tohoku showed two interesting features that are difficult to attribute to only local genetic differentiation. First, within the Hondo cluster, the individuals from Tohoku were closest to the individuals from Okinawa with respect to Eigenvector 1 (Supplemental Data). Second, the FST value between Tohoku and Okinawa was smaller than the FST value between Tokai-Hokuriku and Okinawa, even though the geographical distance between Okinawa and Tohoku is greater than that between Okinawa and Tokai-Hokuriku. These observations might reflect ancient population affinities between Tohoku and Okinawa, which have been obscured by the gene flow between their geographic neighbors in Honshu Island. The presence of two main clusters may also be explained by the long-term isolation of populations in the Ryukyu Islands.34 However, the finding that the FST value between Okinawa and Tohoku was smaller than that between Okinawa and Tokai-Hokuriku cannot be explained by only local genetic differentiation. The distinct difference between the Hondo and the Ryukyu clusters is probably due to two factors: there were two major migrations to Japan, and populations in the Ryukyu Islands became genetically differentiated by isolation.
Although we classified the 7001 Japanese individuals into the two main clusters, most of the individuals in the Hondo cluster were located in a limited area in the PCA plot (between −0.02 and 0.01 for the first component and between −0.02 and 0.02 for the second component). If we define a “core Hondo-cluster area” as this area including most of the individuals, we notice a small fraction of individuals who were located between the Han-Chinese cluster and the core Hondo-cluster area (Figure 3A). Some of those individuals might be genetically non-Japanese East Asians, and others may have mixed Japanese and non-Japanese East-Asian ancestries. Further analyses including individuals from other areas of Asia would be desirable for understanding the Japanese population structure in detail, considering recent migrations from neighboring countries.
It is interesting that the genotype frequencies of two nonsynonymous SNPs, one in EDAR and the other inABCC11, were significantly different between the Hondo and Ryukyu clusters. This is because these SNPs were associated with phenotypic variations, 30 and 31 and it was suggested that the increase in the frequencies of the specific alleles were driven by positive selection. These observations suggest that a search for differentiated nonsynonymous SNPs between closely related subpopulations, like the Hondo and the Ryukyu clusters, would be an efficient approach to finding SNPs that are involved in phenotypic variations and have been under natural selection.
We should be careful when inferring from allele–trait associations that are detected in the genomic regions where relatively higher differentiations were observed (e.g., particular regions in chromosome 6).3 As a result of the considerable heterogeneity in the level of genetic differentiation over the human genome,35 and 36spurious associations are more likely to occur in differentiated regions than in other regions, even if the value of the genome-wide inflation factor is within an acceptable range. To avoid possible false-positive results at differentiated SNPs, a method for correcting the effect of population stratification (implemented in the EIGENSTRAT program in EIGENSOFT13) would be effective.
Because of the genetic differentiation among geographical regions in Japan, the design of a GWAS needs to take into account the structure of the Japanese population, especially if there are differences in disease prevalence among geographical regions of Japan. In the present study, we used individual genotype data to conduct simulations in order to examine to what extent the population stratification causes an increase of false-positive rates in association studies. On the basis of the genome-wide χ2 inflation factor, λ, we found the conditions under which an increase of false-positive rates would be acceptable or negligible. More generally, we propose the following approaches to avoidance of an inflation of false positive rates in a GWAS for the Japanese population: (1) If either cases or controls include individuals from the Ryukyu cluster in different but small proportions, simply exclude them in the studies. (2) If both case and control groups include significant proportions of individuals from the Ryukyu cluster, examine the heterogeneity of the odds ratios among the clusters and the entire sample (e.g., by using the Mantel-Haenzel’s test37). (3) Select controls so that the proportions of individuals from the Ryukyu cluster in case and control groups are as equal as possible. (4) If one examines the relatedness between case and control groups by any method (e.g., the smartpca program in EIGENSOFT,13 and 15 PLINK14) and obtains a result in a two-dimensional graph, then select the controls so that the graph areas including cases and controls are equivalent.
For possible Near Eastern or Middle Eastern components of Okinawan DNA, see also:
Genetic affinity between the Cretans and Okinawans makes a case for ancient connections with Cretan populations because of the presence of “Y haplogroup J/J2 (not to be confused with mtDNA haplogroup J/J2) … J2 #1 appears to reach a significant rate of frequency in Okinawa at 1.15%(see J/J2 charts)”… and “E1b1b (formerly E3b) ,… which reaches a significant rate of frequency at 1.15%”. E1b1b “spread to the Middle East during the Upper Paleolithic and Mesolithic periods,” and “…reaches its highest European concentration in Albania, Kosovo, and northwest Greece”. “J1 #1 reaches its highest rate of frequency in Crete, at 12.50%, J2 #4 reaches its highest rate of frequency in Han China at 2.86%” “It is believed that J2 spread from Anatolia to Greece between the late Neolithic period and the Bronze Age. The Greeks and the Etruscans were primarily responsible for the spread of J2 in the southern and western Mediterranean regions, which included Assyria, Babylonia, and Phoenicia.”