The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank

Abstract

While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5–10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n = 2067), hallucinations (n = 6689), and any psychotic experience (delusions or hallucinations; n = 7803) in 157,366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), bipolar disorder (PRSBP), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in 144,818 UK Biobank participants of European ancestry to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were associated with psychotic experiences (p < 1.77 × 10−5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p < 1.99 × 10−3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD (but not PRSSCZ or PRSBP) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p < 0.002). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study

“…Another study using the PRS-SZ and conducted in adults looked for interaction with other environmental factors, i.e. smoking status, without finding any GxE interaction (García-González et al, 2020). One hypothesis to explain the negative results of this GxE interaction study is that the PRS-SZ is not the appropriate tool for the study of GxE interaction in psychosis (Assary et al, 2018).…”

“…Another study using the PRS-SZ and conducted in adults looked for interaction with other environmental factors, i.e. smoking status, without finding any GxE interaction (García-González et al ., 2020 ).…”

“…In a recent study from EU-GEI WP6 ('Vulnerability and Severity') sample, van Os et al (2020) did not find any associations between PRS-SZ and the 3 dimensions of the CAPE in the controls (without psychotic disorders), although among siblings, a significant association with the negative dimension was found. Among the different studies on association between the PRS-SZ and subclinical psychosis, UK Biobank represents the most closely related to EU-GEI (sample from the general population from United Kingdom), and two of the three studies conducted in UK Biobank found significant associations (Legge et al, 2019;García-González et al, 2020), contrary to the third, that did not find any significant difference (Alloza et al, 2020). Of note, in these 3 UK Biobank studies, the samples were different, especially according to the available data of each subject (e.g.…”

“…A recent study assessing the associations between momentary stress and subclinical psychotic symptoms showed that higher levels of PRS-SZ were associated with a higher intensity of symptoms after a momentary stress among controls (Schick et al ., 2022 ). In the fourth study, the authors assessed the interaction between PRS-SZ and smoking status, but did not show significant association (García-González et al ., 2020 ).…”

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study

“…A recent study assessing the associations between momentary stress and subclinical psychotic symptoms showed that higher levels of PRS-SZ were associated with a higher intensity of symptoms after a momentary stress among controls (Schick et al, 2022). In the fourth study, the authors assessed the interaction between PRS-SZ and smoking status, but did not show significant association (García-González et al, 2020).…”