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

Bochao Danae Lin; Jentien M. Vermeulen; Genetic Risk and Outcome of Psychosis (GROUP) investigators; K. Bolhuis; Xiao Chang; Frederike Schirmbeck; Kristel R. van Eijk; Behrooz Z. Alizadeh; Agna A. Bartels-Velthuis; Therese van Amelsvoort; Richard Bruggeman; Wiepke Cahn; Lieuwe de Haan; Bart P.F. Rutten; Sinan Guloksuz; Jurjen J. Luykx; Jim van Os; Claudia J.P. Simons; Ruud van Winkel; Matthijs Blankers; W. van den Brink

doi:10.1016/j.psychres.2023.115143

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

Bochao Danae Lin, Jentien M. Vermeulen, Genetic Risk and Outcome of Psychosis (GROUP) investigators, K. Bolhuis, Xiao Chang, Frederike Schirmbeck, Kristel R. van Eijk, Behrooz Z. Alizadeh, Agna A. Bartels-Velthuis, Therese van Amelsvoort, Richard Bruggeman, Wiepke Cahn, Lieuwe de Haan, Bart P.F. Rutten, Sinan Guloksuz, Jurjen J. Luykx^*, Jim van Os, Claudia J.P. Simons, Ruud van Winkel, Matthijs BlankersW. van den Brink

^*Corresponding author for this work

Child and Adolescent Psychiatry / Psychology

Research output: Contribution to journal › Article › Academic › peer-review

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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, PRSs-smoking 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 language	English
Article number	115143
Journal	Psychiatry Research
Volume	323
DOIs	https://doi.org/10.1016/j.psychres.2023.115143
Publication status	Published - May 2023

Bibliographical note

Funding Information:
The infrastructure for the GROUP study is funded through the Geestkracht programme of the Dutch Health Research Council (ZonMw, grant number 10-000-1001 ), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organizations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre , GGZ Noord Holland Noord. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical center The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta).

Publisher Copyright: © 2023

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Lin, B. D., Vermeulen, J. M., Genetic Risk and Outcome of Psychosis (GROUP) investigators, Bolhuis, K., Chang, X., Schirmbeck, F., van Eijk, K. R., Alizadeh, B. Z., Bartels-Velthuis, A. A., van Amelsvoort, T., Bruggeman, R., Cahn, W., de Haan, L., Rutten, B. P. F., Guloksuz, S., Luykx, J. J., van Os, J., Simons, C. J. P., van Winkel, R., ... van den Brink, W. (2023). Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls. Psychiatry Research, 323, Article 115143. https://doi.org/10.1016/j.psychres.2023.115143

@article{4b3cd2f880844146a9bf750c6e8e51f0,

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

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, PRSs-smoking 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.",

author = "Lin, \{Bochao Danae\} and Vermeulen, \{Jentien M.\} and \{Genetic Risk and Outcome of Psychosis (GROUP) investigators\} and K. Bolhuis and Xiao Chang and Frederike Schirmbeck and \{van Eijk\}, \{Kristel R.\} and Alizadeh, \{Behrooz Z.\} and Bartels-Velthuis, \{Agna A.\} and \{van Amelsvoort\}, Therese and Richard Bruggeman and Wiepke Cahn and \{de Haan\}, Lieuwe and Rutten, \{Bart P.F.\} and Sinan Guloksuz and Luykx, \{Jurjen J.\} and \{van Os\}, Jim and Simons, \{Claudia J.P.\} and \{van Winkel\}, Ruud and Matthijs Blankers and \{van den Brink\}, W.",

note = "Funding Information: The infrastructure for the GROUP study is funded through the Geestkracht programme of the Dutch Health Research Council (ZonMw, grant number 10-000-1001 ), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organizations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre , GGZ Noord Holland Noord. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical center The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = may,

doi = "10.1016/j.psychres.2023.115143",

language = "English",

volume = "323",

journal = "Psychiatry Research",

issn = "0165-1781",

publisher = "Elsevier Ireland Ltd",

}

Lin, BD, Vermeulen, JM, Genetic Risk and Outcome of Psychosis (GROUP) investigators, Bolhuis, K, Chang, X, Schirmbeck, F, van Eijk, KR, Alizadeh, BZ, Bartels-Velthuis, AA, van Amelsvoort, T, Bruggeman, R, Cahn, W, de Haan, L, Rutten, BPF, Guloksuz, S, Luykx, JJ, van Os, J, Simons, CJP, van Winkel, R, Blankers, M & van den Brink, W 2023, 'Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls', Psychiatry Research, vol. 323, 115143. https://doi.org/10.1016/j.psychres.2023.115143

Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls. / Lin, Bochao Danae; Vermeulen, Jentien M.; Genetic Risk and Outcome of Psychosis (GROUP) investigators et al.
In: Psychiatry Research, Vol. 323, 115143, 05.2023.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls

AU - Lin, Bochao Danae

AU - Vermeulen, Jentien M.

AU - Genetic Risk and Outcome of Psychosis (GROUP) investigators

AU - Bolhuis, K.

AU - Chang, Xiao

AU - Schirmbeck, Frederike

AU - van Eijk, Kristel R.

AU - Alizadeh, Behrooz Z.

AU - Bartels-Velthuis, Agna A.

AU - van Amelsvoort, Therese

AU - Bruggeman, Richard

AU - Cahn, Wiepke

AU - de Haan, Lieuwe

AU - Rutten, Bart P.F.

AU - Guloksuz, Sinan

AU - Luykx, Jurjen J.

AU - van Os, Jim

AU - Simons, Claudia J.P.

AU - van Winkel, Ruud

AU - Blankers, Matthijs

AU - van den Brink, W.

N1 - Funding Information: The infrastructure for the GROUP study is funded through the Geestkracht programme of the Dutch Health Research Council (ZonMw, grant number 10-000-1001 ), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organizations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre , GGZ Noord Holland Noord. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical center The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). Publisher Copyright: © 2023

PY - 2023/5

Y1 - 2023/5

N2 - 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, PRSs-smoking 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.

AB - 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, PRSs-smoking 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.

UR - https://www.scopus.com/pages/publications/85150443563

U2 - 10.1016/j.psychres.2023.115143

DO - 10.1016/j.psychres.2023.115143

M3 - Article

C2 - 36948018

AN - SCOPUS:85150443563

SN - 0165-1781

VL - 323

JO - Psychiatry Research

JF - Psychiatry Research

M1 - 115143

ER -

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

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