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<p>Gestational diabetes mellitus (GDM) is common in Japanese women, posing serious risks to mothers and offspring. This study investigated the influence of maternal genotypes on the risk of GDM and examined how these genotypes modify the effects of psychological and dietary factors during pregnancy. We analyzed data from 20,399 women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort. Utilizing two customized SNP arrays for the Japanese population (Affymetrix Axiom Japonica Array v2 and NEO), we performed a meta-analysis to combine the datasets. Gene-environment interactions were assessed by modeling interaction terms between genome-wide significant single nucleotide polymorphisms (SNPs) and psychological and dietary factors. Our analysis identified two SNP variants, rs7643571 (<i>p </i>= 9.14 × 10<sup>−9</sup>) and rs140353742 (<i>p </i>= 1.24 × 10<sup>−8</sup>), located in an intron of the <i>MDFIC2</i> gene, as being associated with an increased risk of GDM. Additionally, although there were suggestive patterns for interactions between these SNPs and both dietary factors (e.g., carbohydrate and fruit intake) and psychological distress, none of the interaction terms remained significant after Bonferroni correction (<i>p </i>&lt; 0.05/8). While nominal significance was observed in some models (e.g., psychological distress, <i>p </i>= 0.04), the data did not provide robust evidence of effect modification on GDM risk once adjusted for multiple comparisons. These findings reveal novel genetic associations with GDM in Japanese women and highlight the importance of gene-environment interactions in its etiology. Given that previous genome-wide association studies (GWAS) on GDM have primarily focused on Western populations, our study provides new insights by examining an Asian population using a population-specific array.</p>

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Genetic effects on gestational diabetes mellitus and their interactions with environmental factors among Japanese women

  • 期刊论文

  • 发表日期：

    2025年3月21日

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  • Tomoki Kawahara,
  • Nobutoshi Nawa,
  • Keiko Murakami,
  • Toshihiro Tanaka,
  • Hisashi Ohseto,
  • Ippei Takahashi,
  • Akira Narita,
  • Taku Obara,
  • Mami Ishikuro,
  • Masatsugu Orui,
  • Aoi Noda,
  • Genki Shinoda,
  • Yuki Nagata,
  • Satoshi Nagaie,
  • Soichi Ogishima,
  • Junichi Sugawara,
  • Shigeo Kure,
  • Kengo Kinoshita,
  • Atsushi Hozawa,
  • Nobuo Fuse,
  • Gen Tamiya,
  • Wendy L. Bennett,
  • Margaret A. Taub,
  • Pamela J. Surkan,
  • Shinichi Kuriyama,
  • Takeo Fujiwara

摘要

Gestational diabetes mellitus (GDM) is common in Japanese women, posing serious risks to mothers and offspring. This study investigated the influence of maternal genotypes on the risk of GDM and examined how these genotypes modify the effects of psychological and dietary factors during pregnancy. We analyzed data from 20,399 women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort. Utilizing two customized SNP arrays for the Japanese population (Affymetrix Axiom Japonica Array v2 and NEO), we performed a meta-analysis to combine the datasets. Gene-environment interactions were assessed by modeling interaction terms between genome-wide significant single nucleotide polymorphisms (SNPs) and psychological and dietary factors. Our analysis identified two SNP variants, rs7643571 (p = 9.14 × 10−9) and rs140353742 (p = 1.24 × 10−8), located in an intron of the MDFIC2 gene, as being associated with an increased risk of GDM. Additionally, although there were suggestive patterns for interactions between these SNPs and both dietary factors (e.g., carbohydrate and fruit intake) and psychological distress, none of the interaction terms remained significant after Bonferroni correction (p < 0.05/8). While nominal significance was observed in some models (e.g., psychological distress, p = 0.04), the data did not provide robust evidence of effect modification on GDM risk once adjusted for multiple comparisons. These findings reveal novel genetic associations with GDM in Japanese women and highlight the importance of gene-environment interactions in its etiology. Given that previous genome-wide association studies (GWAS) on GDM have primarily focused on Western populations, our study provides new insights by examining an Asian population using a population-specific array.