Whole-exome sequencing in a Chinese sample provides preliminary evidence for the link between rare/low-frequency immune-related variants and early-onset schizophrenia
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AbstractRare and low-frequency variants contribute to schizophrenia (SCZ), and may influence its age-at-onset (AAO). We examined the association of rare or low-frequency deleterious coding variants in Chinese patients with SCZ. We collected DNA samples in 197 patients with SCZ spectrum disorder and 82 healthy controls (HC), and performed exome sequencing. The AAO variable was ascertained in the majority of SCZ participants for identify the early-onset (EOS, AAO<=18) and adult-onset (AOS, AAO>18) subgroups. We examined the overall association of rare/low-frequency, damaging variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels using Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was conducted. Resampling was used to obtain empirical p-values and to control for family-wise error rate (FWER). In binary-trait association tests, we identified 5 potential candidate risk genes and 10 gene ontology biological processes (GOBP) terms, among which PADI2 reached FWER-adjusted significance. In quantitative rare-variant association tests, we found marginally significant correlations of AAO with alterations in 4 candidate risk genes, and 5 GOBP pathways. Together, the biological and functional profiles of these genes and gene sets supported the involvement of perturbations of neural systems in SCZ, and altered immune functions in EOS.
All Author(s) ListZhong Y, Tubbs JD, Leung PBM, Zhan N, Hui TCK, Ho KKY, Hung KSY, Cheung EFC, So HC, Lui SSY, Sham PC
Journal nameAsian Journal of Psychiatry
Year2024
Month6
Volume Number96
PublisherElsevier
Article number104046
ISSN1876-2018
eISSN1876-2026
LanguagesEnglish-United Kingdom
KeywordsAge at onset, Chinese setting, Immune response, Neural perturbation, Schizophrenia, Whole-exome sequencing
