Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls

B.D. Lin, J.M. Vermeulen, K. Bolhuis, X. Chang, F. Schirmbeck, K.R. van Eijk, S. Guloksuz, M. Blankers, W. van den Brink, L. de Haan, J.J. Luykx*, Genetic Risk and Outcome of Psychosis (GROUP) Investigators, Thérèse van Amelsvoort, Bart Rutten, Claudia Simons, Ruud van Winkel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSssmoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms.
Original languageEnglish
Article number115143
Number of pages8
JournalPsychiatry Research
Volume323
Issue number1
DOIs
Publication statusPublished - 1 May 2023

Keywords

  • Polygenic
  • Smoking
  • Schizophrenia
  • Psychosis
  • Positive symptoms
  • Negative symptoms
  • METAANALYSIS
  • WORLDWIDE
  • RISK

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