Triangulation supports agricultural spread of the Transeurasian languages.

The origin and early dispersal of speakers of Transeurasian languages-that is, Japanese, Korean, Tungusic, Mongolic and Turkic-is among the most disputed issues of Eurasian population history1-3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. Here we address this question by 'triangulating' genetics, archaeology and linguistics in a unified perspective. We report wide-ranging datasets from these disciplines, including a comprehensive Transeurasian agropastoral and basic vocabulary; an archaeological database of 255 Neolithic-Bronze Age sites from Northeast Asia; and a collection of ancient genomes from Korea, the Ryukyu islands and early cereal farmers in Japan, complementing previously published genomes from East Asia. Challenging the traditional 'pastoralist hypothesis'6-8, we show that the common ancestry and primary dispersals of Transeurasian languages can be traced back to the first farmers moving across Northeast Asia from the Early Neolithic onwards, but that this shared heritage has been masked by extensive cultural interaction since the Bronze Age. As well as marking considerable progress in the three individual disciplines, by combining their converging evidence we show that the early spread of Transeurasian speakers was driven by agriculture.

Natural Selection Signatures in the Hondo and Ryukyu Japanese Subpopulations.

Natural selection signatures across Japanese subpopulations are under-explored. Here we conducted genome-wide selection scans with 622,926 single nucleotide polymorphisms for 20,366 Japanese individuals, who were recruited from the main-islands of Japanese Archipelago (Hondo) and the Ryukyu Archipelago (Ryukyu), representing two major Japanese subpopulations. The integrated haplotype score (iHS) analysis identified several signals in one or both subpopulations. We found a novel candidate locus at IKZF2, especially in Ryukyu. Significant signals were observed in the major histocompatibility complex region in both subpopulations. The lead variants differed and demonstrated substantial allele frequency differences between Hondo and Ryukyu. The lead variant in Hondo tags HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01, a haplotype specific to Japanese and Korean. While in Ryukyu, the lead variant tags DRB1*15:01-DQB1*06:02, which had been recognized as a genetic risk factor for narcolepsy. In contrast, it is reported to confer protective effects against type 1 diabetes and human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. The FastSMC analysis identified 8 loci potentially affected by selection within the past 20-150 generations, including 2 novel candidate loci. The analysis also showed differences in selection patterns of ALDH2 between Hondo and Ryukyu, a gene recognized to be specifically targeted by selection in East Asian. In summary, our study provided insights into the selection signatures within the Japanese and nominated potential sources of selection pressure.

Demographic history of Ryukyu islanders at the southern part of the Japanese Archipelago inferred from whole-genome resequencing data.

The Ryukyu Islands are located in the southernmost part of the Japanese Archipelago and consist of several island groups. Each island group has its own history and culture, which differ from those of mainland Japan. People of the Ryukyu Islands are genetically subdivided; however, their detailed demographic history remains unclear. We report the results of a whole-genome sequencing analysis of a total of 50 Ryukyu islanders, focusing on genetic differentiation between Miyako and Okinawa islanders. We confirmed that Miyako and Okinawa islanders cluster differently in principal component analysis and ADMIXTURE analysis and that there is a population structure among Miyako islanders. The present study supports the hypothesis that population differentiation is primarily caused by genetic drift rather than by differences in the rate of migration from surrounding regions, such as the Japanese main islands or Taiwan. In addition, the genetic cline observed among Miyako and Okinawa islanders can be explained by recurrent migration beyond the bounds of these islands. Our analysis also suggested that the presence of multiple subpopulations during the Neolithic Ryukyu Jomon period is not crucial to explain the modern Ryukyu populations. However, the assumption of multiple subpopulations during the time of admixture with mainland Japanese is necessary to explain the modern Ryukyu populations. Our findings add insights that could help clarify the complex history of populations in the Ryukyu Islands.

Fine-Scale Genetic Structure and Demographic History in the Miyako Islands of the Ryukyu Archipelago.

The Ryukyu Archipelago is located in the southwest of the Japanese islands and is composed of dozens of islands, grouped into the Miyako Islands, Yaeyama Islands, and Okinawa Islands. Based on the results of principal component analysis on genome-wide single-nucleotide polymorphisms, genetic differentiation was observed among the island groups of the Ryukyu Archipelago. However, a detailed population structure analysis of the Ryukyu Archipelago has not yet been completed. We obtained genomic DNA samples from 1,240 individuals living in the Miyako Islands, and we genotyped 665,326 single-nucleotide polymorphisms to infer population history within the Miyako Islands, including Miyakojima, Irabu, and Ikema islands. The haplotype-based analysis showed that populations in the Miyako Islands were divided into three subpopulations located on Miyakojima northeast, Miyakojima southwest, and Irabu/Ikema. The results of haplotype sharing and the D statistics analyses showed that the Irabu/Ikema subpopulation received gene flows different from those of the Miyakojima subpopulations, which may be related with the historically attested immigration during the Gusuku period (900 - 500 BP). A coalescent-based demographic inference suggests that the Irabu/Ikema population firstly split away from the ancestral Ryukyu population about 41 generations ago, followed by a split of the Miyako southwest population from the ancestral Ryukyu population (about 16 generations ago), and the differentiation of the ancestral Ryukyu population into two populations (Miyako northeast and Okinawajima populations) about seven generations ago. Such genetic information is useful for explaining the population history of modern Miyako people and must be taken into account when performing disease association studies.

Genetic basis for the evolution of pelvic-fin brooding, a new mode of reproduction, in a Sulawesian fish.

Modes of reproduction in animals are diverse, with different modes having evolved independently in multiple lineages across a variety of taxa. However, an understanding of the genomic change driving the transition between different modes of reproduction is limited. Several ricefishes (Adrianichthyidae) on the island of Sulawesi have a unique mode of reproduction called "pelvic-fin brooding," wherein females carry externally fertilized eggs until hatching using their pelvic fins. Phylogenomic analysis demonstrated pelvic-fin brooders to have evolved at least twice in two distant clades of the Adrianichthyidae. We investigated the genetic architecture of the evolution of this unique mode of reproduction. Morphological analyses and laboratory observations revealed that females of pelvic-fin brooders have longer pelvic fins and a deeper abdominal concavity, and that they can carry an egg clutch for longer than nonbrooding adrianichthyids, suggesting that these traits play important roles in this reproductive mode. Quantitative trait locus mapping using a cross between a pelvic-fin brooder Oryzias eversi and a nonbrooding O. dopingdopingensis reveals different traits involved in pelvic-fin brooding to be controlled by different loci on different chromosomes. Genomic analyses of admixture detected no signatures of introgression between two lineages with pelvic-fin brooders, indicating that introgression is unlikely to be responsible for repeated evolution of pelvic-fin brooding. These findings suggest that multiple independent mutations may have contributed to the convergent evolution of this novel mode of reproduction.

[Hemobilia due to ruptured superior pancreaticoduodenal pseudoaneurysm after chemoradiotherapy for pancreatic head cancer: an autopsy case report].

A 78-year-old man came to our department because of obstructive jaundice, and was diagnosed as pancreatic head cancer. He underwent chemoradiation therapy. A metal stent was inserted into the common bile duct and the patient was followed up on an outpatient basis. The patient visited our emergency department 46 days after stent insertion due to abdominal pain. The patient was diagnosed with ruptured pseudoaneurysm of the superior pancreaticoduodenal artery by angiography and treated with coil embolization. He died due to sudden deterioration the next day. Pathological autopsy revealed that the cause of the ruptured pseudoaneurysm appeared to be vasculopathy due to radiation therapy.

Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex.

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.

Species divergence and repeated ancient hybridization in a Sulawesian lake system.

An increasing volume of empirical studies demonstrated that hybridization between distant lineages may have promoted speciation in various taxa. However, the timing, extent and direction of introgressive hybridization remain unknown in many cases. Here, we report a possible case in which repeated hybridization promoted divergence of Oryzias ricefishes (Adrianichthyidae) on Sulawesi, an island of Wallacea. Four Oryzias species are endemic to the Malili Lake system in central Sulawesi, which is composed of five tectonic lakes; of these, one lake is inhabited by two species. Morphological and population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that these two sympatric species are phylogenetically sister to but substantially reproductively isolated from each other. Analyses of admixture and comparison of demographic models revealed that the two sympatric species experienced several substantial introgressions from outgroup populations that probably occurred soon after they had secondary contact with each other in the lake. However, the ratio of migrants from the outgroups was estimated to be different between the two species, which is consistent with the hypothesis that these introgressions aided their divergence or prevented them from forming a hybrid swarm. Repeated lake fragmentations and fusions may have promoted diversification of this freshwater fish species complex that is endemic to this ancient lake system.

Mesozoic origin and 'out-of-India' radiation of ricefishes (Adrianichthyidae).

The Indian subcontinent has an origin geologically different from Eurasia, but many terrestrial animal and plant species on it have congeneric or sister species in other parts of Asia, especially in the Southeast. This faunal and floral similarity between India and Southeast Asia is explained by either of the two biogeographic scenarios, 'into-India' or 'out-of-India'. Phylogenies based on complete mitochondrial genomes and five nuclear genes were undertaken for ricefishes (Adrianichthyidae) to examine which of these two biogeographic scenarios fits better. We found that Oryzias setnai, the only adrianichthyid distributed in and endemic to the Western Ghats, a mountain range running parallel to the western coast of the Indian subcontinent, is sister to all other adrianichthyids from eastern India and Southeast-East Asia. Divergence time estimates and ancestral area reconstructions reveal that this western Indian species diverged in the late Mesozoic during the northward drift of the Indian subcontinent. These findings indicate that adrianichthyids dispersed eastward 'out-of-India' after the collision of the Indian subcontinent with Eurasia, and subsequently diversified in Southeast-East Asia. A review of geographic distributions of 'out-of-India' taxa reveals that they may have largely fuelled or modified the biodiversity of Eurasia.

The effects of intensive oral care before surgery for gastric cancer patients.

OBJECTIVES: Oral function management has been recognized as important strategy for preventing postoperative complications. In this historical cohort study, we focused on the patients who planed gastrectomy, and investigated the appropriate duration and frequency of preoperative oral care to prevent complications after surgery. METHODS: Patients who planed surgery for gastric cancer between 2012 and 2018 were enrolled. We defined intensive oral care (IOC) as initial intervention at least three weeks before surgery and follow-up intervention within a week before surgery. As the primary outcome, the incidence of postoperative infectious complications was compared between the IOC and non-intensive oral care groups. RESULTS: A total of 576 patients were enrolled, including 66 with IOC. The incidence of infectious complications was 2/66 (3.0%) in the IOC group and 64/510 (12.5%) in the non-intensive oral care group. After adjusting for confounding factors, patients with IOC exposure had a lower chance of developing postoperative infectious complications (odds ratio; 0.217, 0.051-0.927). CONCLUSIONS: Intensive oral care can help prevent postoperative infectious complications after gastrectomy. These findings suggest that appropriate preoperative oral care includes at least two interventions: three weeks or more before and within one week before surgery.

Clinical impact of periodontal disease on postoperative complications in gastrointestinal cancer patients.

BACKGROUND: The effectiveness of perioperative oral management in gastrointestinal surgery remains unclear. To elucidate the clinical significance of oral care, we investigated the relationship between the oral environment and postoperative infectious complications (POICs) in patients undergoing gastrointestinal surgery. METHODS: This was a single-institute and historical cohort study of 341 patients. The participants were isolated from consecutive patients undergoing planned radical resection for gastrointestinal carcinoma from January 2016 to June 2017. Dentists assessed the oral environment for periodontal disease, hygiene status, dry mouth, fur on tongue, and tooth stumps. All patients received scaling and tooth brushing instructions. A stepwise logistic regression analysis was conducted to identify risk factors for POICs among the different oral statuses. RESULTS: The surgical procedures performed were gastrectomy in 123 (36.1%), colorectal resection in 185 (54.2%), and pancreatoduodenectomy or others in 38 (11.1%). POICs occurred in 48 patients (14.1%), including deep organ space infection in 20, surgical site infection in 11, anastomotic leakage in 5, urinary tract infection in 4, pneumonia in 2, and others in 6. After adjusting for confounding factors, periodontal disease was isolated as an independent risk factor for POICs (odds ratio 2.091, p = 0.037, 95% confidence interval 1.045-4.183). Other variables of oral environment such as hygiene status, dry mouth, fur on tongue, and tooth stumps did not have a significant impact on POICs. CONCLUSIONS: Periodontal disease is a risk factor for infectious complications after gastrointestinal surgery.

Biomedical and genetic characteristics of the Ryukyuans: demographic history, diseases and physical and physiological traits.

Context: The Ryukyu Islands stretch across a southwestern area of the Japanese Archipelago. Because of their unique geographical and historical backgrounds, Ryukyuans have their own genetic and phenotypic characteristics, which have been disclosed in previous anthropological and biomedical studies. Objective: The history, peopling and biomedical and genetic characteristics of Ryukyuans are reviewed and future research directions are discussed. Conclusion: Morphological and genetic studies have suggested the complex demographic history of Ryukyuans and their relationships with other Asian populations. Knowledge of population formation processes is important to understand the distribution of pathogens. In viral infectious diseases, some strains that may be associated with disease symptoms are specific to Ryukyuans. Dramatic changes in diet have played an important role among Ryukyuans in terms of increases in lifestyle-related diseases and mortality risks. To achieve a better understanding of pathogenic disease factors, further integration of findings regarding the genetic and biomedical characteristics of the Ryukyuans is needed.

Mitochondrial DNA variations in Austronesian-speaking populations living in the New Georgia Islands, the Western Province of the Solomon Islands.

Modern Austronesian (AN)-speaking Melanesians are considered to be derived from the admixture of indigenous non-Austronesian (NAN)-speaking people and AN-speaking people from Southeast Asia. In this study, we analyzed mitochondrial DNA (mtDNA) variations in the D-loop region for two AN-speaking Melanesian populations (Munda and Kusaghe) and an AN-speaking Micronesian population (Rawaki) in the New Georgia Islands, the Western Province of the Solomon Islands to examine their genetic similarities to AN-speaking Polynesians in Tonga and NAN-speaking Melanesians, Gidra, in Papua New Guinea. The 'Polynesian motif', which is well-characterized mtDNA marker for Polynesians, was frequently observed in Munda and Kusaghe. Of particular interest, haplogroup E1a2 + 16261, which has been rarely observed in the Solomon Islands, accounted for 12.8% in Kusaghe. It has been reported that the haplogroup E1a2 arose in Island Southeast Asia (ISEA) 9400 ± 2850 years ago. Phylogenetic and principle component analyses for 24 Oceanian populations revealed that Munda and Kusaghe populations were genetically close to Tongan population, but not to Gidra. Rawaki population showed no apparent genetic similarities to populations of Tonga and Gidra. Our results suggest that considerable gene flow from AN-speaking populations originated from Southeast Asia to indigenous Melanesians occurred in the New Georgia Islands.

Association between the FGFR1 rs13317 single nucleotide polymorphism and orbitale-nasion depth based on cephalometric images.

The fibroblast growth factor receptor 1 (FGFR1) gene plays an important role in craniofacial morphogenesis. In our previous study, an association between FGFR1 single nucleotide polymorphisms (SNPs) and craniofacial morphology was demonstrated in Japanese and Korean subjects. The present study aimed to evaluate the relationship between a common FGFR1 SNP (rs13317) with craniofacial morphology, increasing the number of measurements and examining Egyptian subjects (n = 191) in addition to the Japanese (n = 211) and Korean (n = 226) subjects. Genotyping for rs13317 was performed using the TaqMan assay, and its associations with 81 craniofacial measurements derived from lateral and posteroanterior cephalograms were analyzed by multiple regression analysis controlling sex and facial size. The results from each of the populations were then statistically combined. In the Egyptian subjects, rs13317 was significantly associated with the nasion-orbitale depth (P = 0.00040), and a suggestive association was also observed in the Japanese (P = 0.037) and Korean subjects (P = 0.045). The combined analysis revealed that only the nasion-orbitale depth showed a significant association (P = 0.000062) and that several measurements showed a suggestive association. Our results strongly indicate that rs13317 is associated with a smaller depth between the nasion and orbitale, representing a relative protrusion of the cheekbones and retrusion of the nasal root. A similar characteristic is also observed in individuals with Pfeiffer syndrome, which is caused by a dysfunctional FGFR1 mutation.

Development of New Antimicrobial Agents from Cationic PG-Surfactants Containing Oligo-Lys Peptides.

Peptide gemini-surfactant (PG-surfactant), a kind of lipopeptide, is composed of a short linker peptide (X) between two alkyl-chain-modified Cys residues and peripheral peptides at the N-terminal (Y) and the C-terminal (Z) sides, respectively, of the alkylated Cys residues. In this study, we developed and examined a series of PG-surfactants containing two C12 saturated alkanes and oligo-Lys, arranged at the X-, Y-, or Z-positions. To arrange oligo-Lys at the Y- or Z-positions, a repeat sequence of -Asp-Lys-Asp-Lys- was used at the X-position. All of the PG-surfactants exhibited high antimicrobial activity against both Gram-positive and -negative bacteria. In addition to high antimicrobial activity, a low hemolysis activity is prerequisite for efficient intravenous administration. Among the synthesized PG-surfactants, those having -(Lys)3- at the Y- or Z-positions, i.e. K3-DKDKC12 and DKDKC12K3, showed reasonably low hemolytic activities. This combination of high antimicrobial activity along with low hemolytic activity is an essential and unique property and has not been previously reported for the synthesized lipopeptides. Further, using scanning electron microscopy (SEM) and N-phenyl-1-naphthylamine (NPN) uptake assay we showed that the antimicrobial activity of these PG-surfactants may be attributed to membrane disruptive mechanisms. Although the PG-surfactants with low hemolytic activity could interact and localize onto red blood cell surfaces and cause slight expansion of cell morphologies, no subsequent penetration occurred. In summary, we describe here the successful development of PG-surfactants having high antibacterial and low hemolytic activity, thus providing a significant molecular platform to develop novel antimicrobial agents.

Spatial relationships of the bronchial arteries to the left recurrent laryngeal nerve in the sub-aortic arch area.

PURPOSE: To safely perform lymphadenectomy in the sub-aortic arch area during esophagectomy for esophageal cancer, we investigated the spatial relationships between the bronchial arteries (BAs) and the left recurrent laryngeal nerve (LRLN). METHODS: For this macro-anatomical study, 72 cadavers were used. RESULTS: Of the 195 dissected BAs, 15 (7.7%) arteries ran dorsally across the LRLN. Such a running pattern of the BA was found in 15 (20.8%) of the 72 cadavers. Fourteen (93.3%) of the 15 arteries ran anteriorly along the left side of the esophagus, and 13 (86.7%) passed further to the lateral side of the left main bronchus to reach the ventral surface of the tracheobronchus; we named this running pattern "Type III". Of the 51 arteries with the Type III pattern, 25.5% ran across the dorsal side of the LRLN. CONCLUSION: Approximately 20% of the cadavers had BAs running dorsally to the LRLN in the sub-aortic arch area. Most of these arteries had the Type III pattern. One-quarter of the BAs with the Type III pattern showed this running pattern. Care must be practiced to safely perform lymphadenectomy for esophageal cancer in patients with Type III BAs.

Association study of CREBRF missense variant (rs373863828:G > A; p.Arg457Gln) with levels of serum lipid profile in the Pacific populations.

BACKGROUND: A missense variant (rs373863828:G > A; p.Arg457Gln) of the CREBRF gene is strongly associated with a higher body mass index (BMI; kg/m2) in Polynesian populations. This variant has also been reported to be associated with lower total cholesterol in Samoans. AIM: The aim of this study is to examine the association of rs373863828:G > A with levels of serum lipids in four Pacific populations. METHODS: A total of 613 adult subjects were recruited from Tonga (Polynesians) and the Solomon Islands (Melanesians and Micronesians). Multiple regression analyses adjusted for age and sex were performed to examine the association of rs373863828 with levels of serum lipids in each population. RESULTS: A significant association of rs373863828:G > A with lower level of HDL-cholesterol was detected in the Tonga population (ß = -3.32 and p-value = 0.030). The expected change in HDL-cholesterol with respect to a single copy of the rs373863828-A allele was 3.32 mg/dL. However, the association between rs373863828-A and lower levels of HDL-cholesterol was not significant after further adjustment for BMI in the Tonga population (ß = -2.32 and p-value = 0.13). CONCLUSIONS: The rs373863828-A allele may not directly affect the level of serum HDL-cholesterol independent of BMI. To confirm the present findings, association studies with large sample sizes and functional analyses are required.

Common polymorphisms in WNT10A affect tooth morphology as well as hair shape.

Hair and teeth are appendages of ectodermal origin, and there are common molecular backgrounds involved in their formation. To date, it has been revealed that a non-synonymous polymorphism in EDAR has effects on the morphological variation in both hair and teeth. Previous association studies have confirmed that single-nucleotide polymorphisms (SNPs) in/near THADA, FRAS1, WNT10A, NAF1 and FGFR2 are associated with hair morphology. In this study, we thus examined whether these SNPs are also associated with dental characteristics. We measured metric dental traits including crown size and also evaluated non-metric dental traits using plaster casts obtained from subjects (272 Japanese and 226 Koreans). DNA samples were prepared from the subjects and genotyped for the hair morphology-associated SNPs. We observed a significant association of crown size with an SNP in WNT10A (rs7349332), but not with SNPs in other genes. Therefore, we further examined four SNPs within and around WNT10A, among which rs10177996 had the strongest association with dental traits. World distribution of the derived allele in rs10177996, which is associated with larger teeth, showed that Eurasians have a higher allele frequency than Africans. Together with previous studies on hair morphology, this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages.

Confounding effects of microbiome on the susceptibility of TNFSF15 to Crohn's disease in the Ryukyu Islands.

Crohn's disease (CD) involves chronic inflammation in the gastrointestinal tract due to dysregulation of the host immune response to the gut microbiome. Even though the host-microbiome interactions are likely contributors to the development of CD, a few studies have detected genetic variants that change bacterial compositions and increase CD risk. We focus on one of the well-replicated susceptible genes, tumor necrosis factor superfamily member 15 (TNFSF15), and apply statistical analyses for personal profiles of genotypes and salivary microbiota collected from CD cases and controls in the Ryukyu Islands, southernmost islands of the Japanese archipelago. Our association test confirmed the susceptibility of TNFSF15 in the Ryukyu Islands. We found that the recessive model was supported to fit the observed genotype frequency of risk alleles slightly better than the additive model, defining the genetic effect on CD if a pair of the chromosomes in an individual consists of all risk alleles. The combined analysis of haplotypes and salivary microbiome from a small set of samples showed a significant association of the genetic effect with the increase of Prevotella, which led to a significant increase of CD risk. However, the genetic effect on CD disappeared if the abundance of Prevotella was low, suggesting the genetic contribution to CD is conditionally independent given a fixed amount of Prevotella. Although our statistical power is limited due to the small sample size, these results support an idea that the genetic susceptibility of TNFSF15 to CD may be confounded, in part, by the increase of Prevotella.

A missense variant, rs373863828-A (p.Arg457Gln), of CREBRF and body mass index in Oceanic populations.

It has been suggested that a 'thrifty' genotype hypothesis can account for high prevalence of obesity in the island populations of Oceania. A recent genome-wide association study revealed that a missense variant, rs373863828-A (p.Arg457Gln), of the CREBRF gene (encoding CREB3 regulatory factor) was associated with an excessive increase in body mass index (BMI) in Samoans. In the present study, the association of rs373863828-A with an increase in BMI was examined in four Austronesian (AN)-speaking populations in Oceania. We found that rs373863828-A was frequently observed (frequency of 0.15) in Tongans (Polynesians), and was strongly associated with higher BMI (P=6.1 × 10-4). A single copy of the rs373863828-A allele increased BMI by 3.09 kg m-2 after adjustment of age and sex. No significant association was detected in the other three AN-speaking populations (Melanesians and Micronesians) living in Solomon Islands. This was probably due to the low allele frequency (0.02-0.06) of rs373863828-A as well as small sample size. The rs373863828-A allele was not found in both AN-speaking and non-AN-speaking Melanesians living in Papua New Guinea. Our results suggest that rs373863828-A of CREBRF, a promising thrifty variant, arose in recent ancestors of AN-speaking Polynesians.