박상현 (삼성융합의과학원, 분당서울대학교병원) | 한빛사논문 > 한빛사

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삼성융합의과학원, 분당서울대학교병원

Nat. Genet., Sep 30 2024, | https://doi.org/10.1038/s41588-024-01933-1 Multivariate genomic analysis of 5 million people elucidates the genetic architecture of shared components of the metabolic syndrome

Sanghyeon Park^1,2, Soyeon Kim^3,4, Beomsu Kim^1,2, Dan Say Kim¹, Jaeyoung Kim^1,2, Yeeun Ahn^1,2, Hyejin Kim¹, Minku Song¹, Injeong Shim¹, Sang-Hyuk Jung⁵, Chamlee Cho^1,2, Soohyun Lim⁶, Sanghoon Hong¹, Hyeonbin Jo¹, Akl C. Fahed^7,8,9,10,11, Pradeep Natarajan^7,8,9,10,11, Patrick T. Ellinor^7,8,9,10,11, Ali Torkamani¹², Woong-Yang Park^1,13, Tae Yang Yu¹⁴, Woojae Myung^2,15,16& Hong-Hee Won^1,13,16

¹Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.

²Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.

³Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

⁴Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

⁵Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

⁶Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, South Korea.

⁷Department of Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA.

⁸Department of Medicine, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.

⁹Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

¹⁰Department of Medicine, Harvard Medical School, Boston, MA, USA.

¹¹Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.

¹²Scripps Research Translational Institute, Scripps Research, La Jolla, CA, USA.

¹³Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

¹⁴Department of Medicine, Division of Endocrinology and Metabolism, Wonkwang Medical Center, Wonkwang University School of Medicine, Iksan, South Korea.

¹⁵Department of Neuropsychiatry, College of Medicine, Seoul National University, Seoul, South Korea.

¹⁶These authors contributed equally: Woojae Myung, Hong-Hee Won.

Corresponding authors

Correspondence to Woojae Myung or Hong-Hee Won.

Abstract

Metabolic syndrome (MetS) is a complex hereditary condition comprising various metabolic traits as risk factors. Although the genetics of individual MetS components have been investigated actively through large-scale genome-wide association studies, the conjoint genetic architecture has not been fully elucidated. Here, we performed the largest multivariate genome-wide association study of MetS in Europe (n_observed = 4,947,860) by leveraging genetic correlation between MetS components. We identified 1,307 genetic loci associated with MetS that were enriched primarily in brain tissues. Using transcriptomic data, we identified 11 genes associated strongly with MetS. Our phenome-wide association and Mendelian randomization analyses highlighted associations of MetS with diverse diseases beyond cardiometabolic diseases. Polygenic risk score analysis demonstrated better discrimination of MetS and predictive power in European and East Asian populations. Altogether, our findings will guide future studies aimed at elucidating the genetic architecture of MetS.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-10-02)
연구진국내(교신)+국외 연구진
분야 생명과학 > 유전학

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