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Understanding the genetic architecture of the metabolically unhealthy normal weight and metabolically healthy obese phenotypes in a Korean population

 Jae-Min Park  ;  Da-Hyun Park  ;  Youhyun Song  ;  Jung Oh Kim  ;  Ja-Eun Choi  ;  Yu-Jin Kwon  ;  Seong-Jin Kim  ;  Ji-Won Lee  ;  Kyung-Won Hong 
 SCIENTIFIC REPORTS, Vol.11(1) : 2279, 2021-01 
Journal Title
Issue Date
Understanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes-metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes.
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1. College of Medicine (의과대학) > Dept. of Family Medicine (가정의학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Yu-Jin(권유진) ORCID logo https://orcid.org/0000-0002-9021-3856
Park, Jae Min(박재민) ORCID logo https://orcid.org/0000-0001-8873-8832
Song, Youhyun(송유현) ORCID logo https://orcid.org/0000-0001-5621-2107
Lee, Ji Won(이지원) ORCID logo https://orcid.org/0000-0002-2666-4249
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