Genome-wide association study based on clustering by obesity-related variables uncovers a genetic architecture of obesity in the Japanese and the UK populations
Ippei Takahashi,
Hisashi Ohseto,
Fumihiko Ueno,
Tomomi Oonuma,
Akira Narita,
Taku Obara,
Mami Ishikuro,
Keiko Murakami,
Aoi Noda,
Atsushi Hozawa,
Junichi Sugawara,
Gen Tamiya,
Shinichi Kuriyama
Affiliations
Ippei Takahashi
Graduate School of Medicine, Tohoku University, Sendai, Japan
Hisashi Ohseto
Graduate School of Medicine, Tohoku University, Sendai, Japan
Fumihiko Ueno
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Tomomi Oonuma
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Akira Narita
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Taku Obara
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Hospital, Sendai, Japan
Mami Ishikuro
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Keiko Murakami
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Aoi Noda
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Tohoku University Hospital, Sendai, Japan
Atsushi Hozawa
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Junichi Sugawara
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
Gen Tamiya
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; RIKEN Center for Advanced Intelligence Project, Tokyo, Japan
Shinichi Kuriyama
Graduate School of Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; International Research Institute of Disaster Science, Tohoku University, Sendai, Japan; Corresponding author. Graduate School of Medicine, Tohoku University, Sendai, Japan.
Whether all obesity-related variants contribute to the onset of obesity or one or a few variants cause obesity in genetically heterogeneous populations remains obscure. Here, we investigated the genetic architecture of obesity by clustering the Japanese and British populations with obesity using obesity-related factors. In Step-1, we conducted a genome-wide association study (GWAS) with body mass index (BMI) as the outcome for eligible participants. In Step-2, we assigned participants with obesity (BMI ≥25 kg/m2) to five clusters based on obesity-related factors. Subsequently, participants from each cluster and those with a BMI <25 kg/m2 were combined. A GWAS was conducted for each cluster.Several previously identified obesity-related genes were verified in Step-1. Of the genes detected in Step-1, unique obesity-related genes were detected separately for each cluster in Step-2. Our novel findings suggest that a smaller sample size with increased homogeneity may provide insights into the genetic architecture of obesity.
