Genome-wide association study and polygenic risk score analysis for schizophrenia in a Korean population

Dongbin Lee; Ji Hyun Baek; Yujin Kim; Byung Dae Lee; Eun-Young Cho; Eun-Jeong Joo; Yong Min Ahn; Se Hyun Kim; Young-Chul Chung; Fatima Zahra Rami; Se Joo Kim; Sung-Wan Kim; Woojae Myung; Tae Hyon Ha; Heon-Jeong Lee; Hayoung Oh; Kyu Young Lee; Min Ji Kim; Chae Yeong Kang; Sumoa Jeon; Anna Jo; Hyeona Yu; Seunghwa Jeong; Kyooseob Ha; Beomsu Kim; Injeong Shim; Chamlee Cho; Hailiang Huang; Hong-Hee Won; Kyung Sue Hong

doi:10.1016/j.ajp.2024.104203

Genome-wide association study and polygenic risk score analysis for schizophrenia in a Korean population

Asian J Psychiatr. 2024 Sep 11:102:104203. doi: 10.1016/j.ajp.2024.104203. Online ahead of print.

Authors

Dongbin Lee¹, Ji Hyun Baek², Yujin Kim¹, Byung Dae Lee³, Eun-Young Cho⁴, Eun-Jeong Joo⁵, Yong Min Ahn⁶, Se Hyun Kim⁶, Young-Chul Chung⁷, Fatima Zahra Rami⁷, Se Joo Kim⁸, Sung-Wan Kim⁹, Woojae Myung¹⁰, Tae Hyon Ha¹⁰, Heon-Jeong Lee¹¹, Hayoung Oh¹², Kyu Young Lee¹³, Min Ji Kim⁶, Chae Yeong Kang⁷, Sumoa Jeon¹⁴, Anna Jo⁹, Hyeona Yu¹⁵, Seunghwa Jeong¹¹, Kyooseob Ha¹⁶, Beomsu Kim¹⁷, Injeong Shim¹, Chamlee Cho¹, Hailiang Huang¹⁸, Hong-Hee Won¹⁹, Kyung Sue Hong²⁰

Affiliations

¹ Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
² Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
³ Pusan National University Research Park, Busan, South Korea.
⁴ Samsung Biomedical Research Institute, Seoul, South Korea.
⁵ Department of Psychiatry, Euijeongbu Eulji University Hospital, Euijeongbu, South Korea; Department of Neuropsychiatry, Eulji University, School of Medicine, Daejeon, South Korea.
⁶ Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
⁷ Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, South Korea; Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, South Korea.
⁸ Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.
⁹ Department of Psychiatry, Chonnam National University Medical School, Gwangju, South Korea.
¹⁰ Department of Psychiatry, Seoul National University, College of Medicine, Seoul, South Korea; Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.
¹¹ Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea.
¹² Pusan National University Research Park, Pusan, South Korea.
¹³ Department of Neuropsychiatry, Eulji University, School of Medicine, Daejeon, South Korea; Department of Psychiatry, Nowon Eulji University Hospital, Seoul, South Korea.
¹⁴ Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.
¹⁵ Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.
¹⁶ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Psychiatry, Lions Gate Hospital - Vancouver Coastal Health Authority, British Columbia, Canada.
¹⁷ Department of Precision Medicine, Sungkyunkwan University, School of Medicine, Seoul, South Korea.
¹⁸ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. Electronic address: hhuang@broadinstitute.org.
¹⁹ Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea. Electronic address: wonhh@skku.edu.
²⁰ Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Psychiatry, Lions Gate Hospital - Vancouver Coastal Health Authority, British Columbia, Canada. Electronic address: kyungsue.hong@ubc.ca.

PMID: 39293130
DOI: 10.1016/j.ajp.2024.104203

Abstract

Although large-scale genome-wide association studies (GWASs) have revealed the genetic architecture of schizophrenia, these studies have mainly focused on populations of European ancestry. This study aimed to identify common genetic variants associated with schizophrenia in the Korean population and evaluate the performance of polygenic risk scores (PRSs) derived from large-scale GWASs across ancestries. In the Korean psychiatric GWAS project (KPGP), seven academic institutes and their affiliated hospitals across South Korea recruited a cohort of 1670 patients with DSM-IV-defined schizophrenia and 2271 healthy controls. A total of 6690,822 SNPs were tested for association with schizophrenia. We identified one previously unreported genome-wide significant locus rs2423464 (P = 2.83 × 10^-11; odds ratio = 1.65; 95 % confidence interval = 1.43-1.91, minor allele frequency = 0.126). This variant was also associated with increased lysosomal-associated membrane protein family member 5 (LAMP5) gene expression. The PRS derived from the meta-analysis results of East Asian and European GWASs explained a larger proportion of the phenotypic variance in the Korean schizophrenia sample than the PRS of an East Asian or European GWAS. (R² = 0.073 for meta-analysis; 0.028 for East Asian GWAS; 0.037 for European GWAS). GWASs involving diverse ethnic groups will expand our understanding of the genetic architecture of schizophrenia.

Keywords: East Asian; Genome-wide association study; Korean; Polygenic risk, Score; Schizophrenia.