TY - JOUR
T1 - Japanese Population Structure, Based on SNP Genotypes from 7003 Individuals Compared to Other Ethnic Groups
T2 - Effects on Population-Based Association Studies
AU - Yamaguchi-Kabata, Yumi
AU - Nakazono, Kazuyuki
AU - Takahashi, Atsushi
AU - Saito, Susumu
AU - Hosono, Naoya
AU - Kubo, Michiaki
AU - Nakamura, Yusuke
AU - Kamatani, Naoyuki
N1 - Funding Information:
We thank Kazuharu Misawa, Takahiro Nakamura, Tatsuhiko Tsunoda, and Ryo Yamada for helpful discussions. We thank Toshihiro Tanaka for his effort in the SNP-discovery project in Japan. We thank all of the members in the Laboratory for Genotyping. We also thank all of the members in the BioBank Japan Project for their efforts in organizing the project. This study was supported by the Ministry of Education, Culture, Sports, Science and Technology; of Japan.
PY - 2008/10/10
Y1 - 2008/10/10
N2 - Because population stratification can cause spurious associations in case-control studies, understanding the population structure is important. Here, we examined Japanese population structure by "Eigenanalysis," using the genotypes for 140,387 SNPs in 7003 Japanese individuals, along with 60 European, 60 African, and 90 East-Asian individuals, in the HapMap project. Most Japanese individuals fell into two main clusters, Hondo and Ryukyu; the Hondo cluster includes most of the individuals from the main islands in Japan, and the Ryukyu cluster includes most of the individuals from Okinawa. The SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were found in the HLA region in chromosome 6. The nonsynonymous SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were the Val/Ala polymorphism (rs3827760) in the EDAR gene, associated with hair thickness, and the Gly/Ala polymorphism (rs17822931) in the ABCC11 gene, associated with ear-wax type. Genetic differentiation was observed, even among different regions in Honshu Island, the largest island of Japan. Simulation studies showed that the inclusion of different proportions of individuals from different regions of Japan in case and control groups can lead to an inflated rate of false-positive results when the sample sizes are large.
AB - Because population stratification can cause spurious associations in case-control studies, understanding the population structure is important. Here, we examined Japanese population structure by "Eigenanalysis," using the genotypes for 140,387 SNPs in 7003 Japanese individuals, along with 60 European, 60 African, and 90 East-Asian individuals, in the HapMap project. Most Japanese individuals fell into two main clusters, Hondo and Ryukyu; the Hondo cluster includes most of the individuals from the main islands in Japan, and the Ryukyu cluster includes most of the individuals from Okinawa. The SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were found in the HLA region in chromosome 6. The nonsynonymous SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were the Val/Ala polymorphism (rs3827760) in the EDAR gene, associated with hair thickness, and the Gly/Ala polymorphism (rs17822931) in the ABCC11 gene, associated with ear-wax type. Genetic differentiation was observed, even among different regions in Honshu Island, the largest island of Japan. Simulation studies showed that the inclusion of different proportions of individuals from different regions of Japan in case and control groups can lead to an inflated rate of false-positive results when the sample sizes are large.
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U2 - 10.1016/j.ajhg.2008.08.019
DO - 10.1016/j.ajhg.2008.08.019
M3 - Article
C2 - 18817904
AN - SCOPUS:53049090475
SN - 0002-9297
VL - 83
SP - 445
EP - 456
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 4
ER -