F4. A PILOT GENETIC STUDY OF ANXIETY IN A MIDDLE-AGED CHINESE POPULATION: COMMON VARIANT AND RARE COPY NUMBER VARIANT ANALYSES

Background Anxiety disorders have a substantial genetic component. However, our understanding of the impact of common and rare variants on anxiety in non-European adult populations remains limited. Methods Between July 2020 and January 2025, 13,451 individuals aged 40-65 years were recruited in the China Surgery and Anaesthesia Cohort (CSAC) and donated blood samples. Anxiety disorder status was defined based on hospital discharge records (December 2019 to July 2025) or self-reported diagnoses/medication use at baseline. Associations with common genetic variants, rare CNVs, and polygenic risk scores (PRS) were assessed. Generalised anxiety symptom severity, defined as the mean score of the Generalised Anxiety Disorder 7-item (GAD-7) scale across baseline and follow-up assessments, was tested for associations with common variants and PRS. Results Among 11,651 participants included in the case-control analyses (6629 women [58.2%]; mean [SD] age, 52.31 [7.16] years), 338 (2.9%) had anxiety disorders. Genome-wide association study (GWAS) of common variants revealed two loci (chr8p12 and chr9p23, the latter located in an intronic region of PTPRD) associated with anxiety disorder risk. No genome-wide significant loci were identified for anxiety symptom severity. PRS for anxiety disorders was positively associated with both case status and symptom severity. Increased CNV burdens–particularly the total number and size of deletions, number of genes affected by deletions, and number of triplo-sensitive genes affected by duplications–was observed in individuals of anxiety disorders. Discussion This work adds evidence on the genetic basis and provides insights into the genetic architecture of anxiety among East Asian populations. The identified GWAS signals and CNV associations warrants future replication in independent samples.