University of the Ryukyus · Faculty of Medicine · 准教授

Research keywordspopulation genomics・ancient DNA・genetic association・targeted sequencing・epigenetics・nutrigenetics・molecular anthropology・genome-wide analysis

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• Sex-specific associations between air pollutants and asthma prevalence in Japanese adults: a population-based study2025 · This study investigated the association between air pollutants and asthma prevalence in male and female Japanese adults. In this retrospective cross-sectional analysis, annual mean exposure levels of air pollutants, specifically nitrogen dioxide (NO2) and particulate matter with a median aerodynamic diameter ≤2.5 μm (PM2.5), were assessed at a local monitoring site. Multivariable logistic regression models, adjusted for genetic and/or lifestyle factors, were used to explore the association between air pollutants and asthma, with stratification by sex. A total of 1,497 participants aged ≥40 years were included. Their mean age was 65.9 ± 12.4 years, with 847 being women. Overall, 91 participants were diagnosed with asthma. In the multivariable model, ambient exposure levels of NO2 and PM2.5 were significantly associated with asthma in women but not in men. This study highlights sex as a significant determinant of the link between air pollutants and asthma exacerbation, particularly among female Japanese adults.
• Identification of potential disease-associated variants in idiopathic generalized epilepsy using targeted sequencing2024 · Many questions remain regarding the genetics of idiopathic generalized epilepsy (IGE), a subset of genetic generalized epilepsy (GGE). We aimed to identify the candidate coding variants of epilepsy panel genes in a cohort of affected individuals, using variant frequency information from a control cohort of the same region. We performed whole-exome sequencing analysis of 121 individuals and 10 affected relatives, focusing on variants of 950 candidate genes associated with epilepsy according to the Genes4Epilepsy curated panel. We identified 168 candidate variants (CVs) in 137 of 950 candidate genes in 88 of 121 affected individuals with IGE, of which 61 were novel variants. Notably, we identified five CVs in known GGE-associated genes (CHD2, GABRA1, RORB, SCN1A, and SCN1B) in five individuals and CVs shared by affected individuals in each of four family cases for other epilepsy candidate genes. The results of this study demonstrate that IGE is a disease with high heterogeneity and provide IGE-associated CVs whose pathogenicity should be proven by future studies, including advanced functional analysis. The low detection rate of CVs in the GGE-associated genes (4.1%) in this study suggests the current incompleteness of the Genes4Epilepsy panel for the diagnosis of IGE in clinical practice.
• Medieval genomes from eastern Mongolia share a stable genetic profile over a millennium2024 · Recent archaeogenomic studies in Mongolia have elucidated the genetic origins of people from the Xiongnu and Mongol eras, but left the Medieval period between them only tangentially explored. Due to this dearth of ancient genomes, the dynamic history of Medieval Mongolia with the rise and fall of numerous polities still lacks a genomic perspective. To fill in this knowledge gap, here we report whole-genome sequences of nine ancient individuals from eastern Mongolia, who were excavated from two nearby cemeteries, Gurvan Dov and Tavan Khailaast. They are distributed from the Xiongnu-Xianbei period (ca. 200 CE) to the Mongol era (ca. 1,400 CE), forming a local time transect encompassing nearly 1,200 years. Remarkably, despite the long-time span, all nine individuals derive most of their ancestry (85–100%) from the eastern Eurasian lineages and show low heterogeneity in their genetic composition. This is in contrast to the general pattern observed in previously published Medieval genomes from central Mongolia, who showed higher heterogeneity and overall less eastern Eurasian ancestry, thus calling for a comprehensive archaeogenetic survey of Medieval Mongolia to fully capture the dynamic genetic history in this period.
• Long-term exposure to diesel exhaust particles induces concordant changes in DNA methylation and transcriptome in human adenocarcinoma alveolar basal epithelial cells2024 · BACKGROUND: Diesel exhaust particles (DEP), which contain hazardous compounds, are emitted during the combustion of diesel. As approximately one-third of the vehicles worldwide use diesel, there are growing concerns about the risks posed by DEP to human health. Long-term exposure to DEP is associated with airway hyperresponsiveness, pulmonary fibrosis, and inflammation; however, the molecular mechanisms behind the effects of DEP on the respiratory tract are poorly understood. Such mechanisms can be addressed by examining transcriptional and DNA methylation changes. Although several studies have focused on the effects of short-term DEP exposure on gene expression, research on the transcriptional effects and genome-wide DNA methylation changes caused by long-term DEP exposure is lacking. Hence, in this study, we investigated transcriptional and DNA methylation changes in human adenocarcinoma alveolar basal epithelial A549 cells caused by prolonged exposure to DEP and determined whether these changes are concordant. RESULTS: DNA methylation analysis using the Illumina Infinium MethylationEPIC BeadChips showed that the methylation levels of DEP-affected CpG sites in A549 cells changed in a dose-dependent manner; the extent of change increased with increasing dose reaching the statistical significance only in samples exposed to 30 µg/ml DEP. Four-week exposure to 30 µg/ml of DEP significantly induced DNA hypomethylation at 24,464 CpG sites, which were significantly enriched for DNase hypersensitive sites, genomic regions marked by H3K4me1 and H3K27ac, and several transcription factor binding sites. In contrast, 9,436 CpG sites with increased DNA methylation levels were significantly overrepresented in genomic regions marked by H3K27me3 as well as H3K4me1 and H3K27ac. In parallel, gene expression profiling by RNA sequencing demonstrated that long-term exposure to DEP altered the expression levels of 2,410 genes, enriching 16 gene sets including Xenobiotic metabolism, Inflammatory response, and Senescence. In silico analysis revealed that the expression levels of 854 genes correlated with the methylation levels of the DEP-affected cis-CpG sites. CONCLUSIONS: To our knowledge, this is the first report of genome-wide transcriptional and DNA methylation changes and their associations in A549 cells following long-term exposure to DEP.

• 古代ゲノム解析による北海道北東部における人類集団史の復元2025 · 基盤研究(B)
• 低カバレッジ古代ゲノムデータの参照バイアスと集団遺伝学的解析への影響の検討2023 · 挑戦的研究(萌芽)
• 生活習慣病の精密医療に向けた多層オミックス解析による新規リスク評価法の開発研究2023 · 基盤研究(B)
• 顔面形態関連遺伝子多型の探索および人類学的応用

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