T75. ASSOCIATIONS BETWEEN POLYGENIC RISK SCORE FOR SCHIZOPHRENIA AND SCHIZOTYPAL TRAITS IN THE MULTIPLEX FAMILIES OF PATIENTS WITH SCHIZOPHRENIA

• Published in: European neuropsychopharmacology 2024-10, Vol.87, p.194-194
• Main Authors: Chen, Wei J., Jen, Ya-Wen, Yu, Sung-Liang, Hsiao, Po-Chang, Yu, Shun-Chun, Liu, Chih-Min, Liu, Chen-Chung, Hwang, Tzung-Jeng, Hsieh, Ming H., Chien, Yi-Ling, Lin, Yi-Ting, Faraone, Stephen V., Tsuang, Ming T., Hwu, Hai-Gwo
• Format: Article
• Language: English
• ISSN: 0924-977X
• DOI: 10.1016/j.euroneuro.2024.08.385

A possible connection between schizotypy and schizophrenia (SZ) might be attributable to their overlapping genetic determinants in terms of the polygenic risk score (PRS). Using multiplex SZ families, this study aims to (1) investigate the relationship of the PRS for SZ (SZ-PRS) and dimensional schizotypal traits, including schizophrenic symptom in the patients with SZ and schizotypy in their unaffected relatives; (2) evaluate the changes of the association patterns of SZ-PRS and dimensional schizotypal traits after combining patients with their unaffected relatives; and (3) examine whether the dimensional schizotypal traits were also associated with PRS for general personality, bipolar disorder (BIP), and major depression disorder (MDD). Among 557 multiplex families recruited in Taiwan Schizophrenia Linkage Study, 1275 individuals were genotyped using Illumina PsychChip array. A total of 538 patients and their 543 unaffected relatives from 315 families, who had passed the quality control and completed the measurements of schizotypal traits, were included for subsequent analyses. A modified Structured Interview for Schizotypy were used for assessing schizotypy factors among unaffected relatives and the Scales for Positive and Negative Symptoms for assessing schizophrenic symptom factors among patients. A PRS was derived first using the summary statistics of the GWAS from the Psychiatric Genomic Consortium-2 SZ cohort as the discovery dataset, and then a weighted sum of SNPs was calculated using the logarithm of each SNP's odds ratio for the effect allele from the discovery dataset. Among the three groups of participants (538 patients, 53 unaffected siblings, and 490 unaffected parents), both patients and unaffected siblings had similar age and educational levels, whereas parents had lower educational levels compared to their offspring. An alignment approach was used to derive the 2-factor schizotypal trait (i.e., the Aligned Positive Schizophrenic-Schizotypy and the Aligned Negative Schizophrenic-Schizotypy factor). We found that the SZ-PRS was correlated only with Disorganization factor from three Schizophrenic symptom factors in the patients as well as with Social isolation/Introversion factor from four Schizotypy factors in their unaffected relatives. Second, after pooling patients and their unaffected relatives, SZ-PRS explained more variance of Aligned Negative Schizophrenic-Schizotypy factor than that of Aligned Positive Schizophrenic-Schizotypy fact