Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan

Wei-De Lin; Ting-Yuan Liu; Yu-Chia Chen; I-Ching Chou; Fuu-Jen Tsai

doi:10.1016/j.bj.2024.100725

Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan

Biomed J. 2024 Apr 10:100725. doi: 10.1016/j.bj.2024.100725. Online ahead of print.

Authors

Wei-De Lin¹, Ting-Yuan Liu², Yu-Chia Chen², I-Ching Chou³, Fuu-Jen Tsai⁴

Affiliations

¹ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.
² Million-person precision medicine initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
³ Division of Pediatrics Neurology, China Medical University Children's Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan. Electronic address: 004009@tool.caaumed.org.tw.
⁴ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Division of Genetics and Metabolism, China Medical University Children's Hospital, Taichung, Taiwan; Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan; Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan. Electronic address: 000704@tool.caaumed.org.tw.

PMID: 38608873
DOI: 10.1016/j.bj.2024.100725

Abstract

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Several susceptibility loci associated with TS have been identified previously in populations of European descent using genome-wide association studies (GWAS). However, the exact pathogenic mechanism underlying TS is unknown; additionally, the results of previous GWAS for TS were based on Western populations, which may not translate to other populations. Therefore, we conducted a GWAS in Taiwanese patients with TS and chronic tic disorders (CTDs), with an aim to elucidate the genetic basis and potential risk factors for TS in this population.

Methods: GWAS was performed on a Taiwanese TS/CTDs cohort with a sample size of 1,007 patients with TS and 25,522 ancestry-matched controls. Additionally, polygenic risk score was calculated and assessed.

Results: Genome-wide significant locus, rs12313062 (p=1.43 × 10^-8) and other 9 single nucleotide polymorphisms, were identified in chromosomes 12q23.2, associated with DRAM1 and was a novel susceptibility locus identified in TS/CTDs group. DRAM1, a lysosomal transmembrane protein regulated by p53, modulates autophagy and apoptosis, with potential implications for neuropsychiatric conditions associated with autophagy disruption.

Conclusions: This study conducted the first GWAS for TS in a Taiwanese population, identifying a significant locus on chromosome 12q23.2 associated with DRAM1. These findings provide novel insights into the neurobiology of TS and potential directions for future research in this area.

Keywords: Genetic Biobank of China Medical University Hospital; Genome-wide association study; Polygenic risk score; Taiwanese; Tourette syndrome.