ORIGINAL RESEARCH ARTICLE The allele frequency of ALDH2*Glu504Lys and ADH1B*Arg47His for the Ryukyu islanders and their history of expansion among East Asians Kae Koganebuchi 1,2 | Kuniaki Haneji 3,7 | Takashi Toma 4,7 | Keiichiro Joh 5 | Hidenobu Soejima 5 | Kazuma Fujimoto 6 | Hajime Ishida 7 | Motoyuki Ogawa 1,8 | Tsunehiko Hanihara 1,8,9 | Shoji Harada 10 | Shoji Kawamura 2 | Hiroki Oota 1,2,8 1 Department of Biological Structure, Kitasato University Graduate School of Medical Sciences, Kanagawa 252-0373, Japan 2 Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba 277-8562, Japan 3 Haneji Oral Surgery Clinic, Medical Corporation Hayamakai, Okinawa 906-0015, Japan 4 Department of Oral and Maxillofacial Surgery, Adventist Medical Center, Okinawa 903-0201, Japan 5 Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan 6 Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan 7 Department of Human Biology and Anatomy, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan 8 Department of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374, Japan 9 The University Museum, The University of Tokyo, Tokyo 113-0033, Japan 10 Ex-Institute of Community Medicine, University of Tsukuba, Ibaraki 305-8575, Japan Correspondence Dr. Hiroki Oota, Department of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374, Japan. Email: hiroki_oota@med.kitasato-u.ac.jp Funding information This work was supported in by Grants-in-Aid for Scientific Research B to HO (24370099 and 21370108), B to HI (22370087), and A to SK (15H02421) from the Japan Society for the Promotion of Science (JSPS), and University of the Ryukyus Strategic Research Grant to HI. KK is supported by the JSPS Fellowship (15J10824). Abstract Objectives: A cline of frequencies of the derived allele of the ALDH2 gene, which causes a deficiency of an enzyme and “facial flushing” in humans who drink alcohol, has been known among the people of the Japanese archipelago. This cline is conven- tionally explained by admixture with immigrants from the Asian continent occurring during the Yayoi period. Previous studies lack sufficient data from the peripheral regions of the indigenous Jomon people, and those data the ADH1B gene that is involved in the Class I ADH gene cluster and contains another variant leading to a functional change. Methods: We focused on the southwestern-most people from the Ryukyu Islands (n 5 218) and those from northern Kyushu (n 5 21) where the Yayoi immigrants likely arrived. We investigated both the Class I ADH and ALDH2 loci, as well as neutral genetic markers. Results: In the Ryukyu Islands, the frequencies of the ancestral alleles in both loci were always higher than those in mainland Japan, while the frequencies of ADH1B were less than those of the derived allele. A haplotype block was not observed in ALDH2 but was in Class I ADH. Discussion: Our data suggest that the derived allele of ALDH2 came with the Yayoi immigrants from the Asian continent to the Japanese archipelago. However, the Am. J. Hum. Biol. 2016; 1-14 wileyonlinelibrary.com/journal/ajhb V C 2016 Wiley Periodicals, Inc. | 1 Received: 23 June 2016 | Revised: 9 September 2016 | Accepted: 4 October 2016 DOI 10.1002/ajhb.22933 American Journal of Human Biology