Genetic determinants of obesity in Korean populations: exploring genome-wide associations and polygenic risk scores.

Autor: Jo J; Department of Public Health Sciences, Graduate school of Public Health, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Ha N; Department of Public Health Sciences, Graduate school of Public Health, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Ji Y; Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Do A; Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Seo JH; Veterans Health Service Medical Center, Veterans Medical Research Institute, 53, Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul, 05368, South Korea., Oh B; Department of Family Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 20, Boramae-ro 5-gil, Dongjak-gu, Seoul, 07061, South Korea., Choi S; Department of Applied Mathematics, Hanyang University (ERICA), 55, Hanyang-deahak-ro, Sangnok-gu, Ansan, Gyeonggi-do, 15588, South Korea., Choe EK; Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.; Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, 39FL, 152, Teheran-ro, Gangnam-gu, Seoul, 06236, South Korea., Lee W; Department of Public Health Sciences, Graduate school of Public Health, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.; Institute of Health and Environment, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Son JW; Division of Endocrinology, Department of Internal Medicine, Bucheon St. Mary's hospital, The Catholic University of Korea, 327, Sosa-ro, Bucheon-si, Gyeonggi-do, Bucheon, 14647, South Korea., Won S; Department of Public Health Sciences, Graduate school of Public Health, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.; Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.; Institute of Health and Environment, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.; RexSoft Corps, Seoul National University Administration Building, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.
Jazyk: angličtina
Zdroj: Briefings in bioinformatics [Brief Bioinform] 2024 Jul 25; Vol. 25 (5).
DOI: 10.1093/bib/bbae389
Abstrakt: East Asian populations exhibit a genetic predisposition to obesity, yet comprehensive research on these traits is limited. We conducted a genome-wide association study (GWAS) with 93,673 Korean subjects to uncover novel genetic loci linked to obesity, examining metrics such as body mass index, waist circumference, body fat ratio, and abdominal fat ratio. Participants were categorized into non-obese, metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) groups. Using advanced computational methods, we developed a multifaceted polygenic risk scores (PRS) model to predict obesity. Our GWAS identified significant genetic effects with distinct sizes and directions within the MHO and MUO groups compared with the non-obese group. Gene-based and gene-set analyses, along with cluster analysis, revealed heterogeneous patterns of significant genes on chromosomes 3 (MUO group) and 11 (MHO group). In analyses targeting genetic predisposition differences based on metabolic health, odds ratios of high PRS compared with medium PRS showed significant differences between non-obese and MUO, and non-obese and MHO. Similar patterns were seen for low PRS compared with medium PRS. These findings were supported by the estimated genetic correlation (0.89 from bivariate GREML). Regional analyses highlighted significant local genetic correlations on chromosome 11, while single variant approaches suggested widespread pleiotropic effects, especially on chromosome 11. In conclusion, our study identifies specific genetic loci and risks associated with obesity in the Korean population, emphasizing the heterogeneous genetic factors contributing to MHO and MUO.
(© The Author(s) 2024. Published by Oxford University Press.)
Databáze: MEDLINE
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