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No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder

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No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder. / Hjorthøj, Carsten; Uddin, Md Jamal; Wimberley, Theresa; Dalsgaard, Søren; Hougaard, David M; Børglum, Anders; Werge, Thomas; Nordentoft, Merete.

I: Psychological Medicine, Bind 51, Nr. 3, 02.2021, s. 479-484.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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Author

Hjorthøj, Carsten ; Uddin, Md Jamal ; Wimberley, Theresa ; Dalsgaard, Søren ; Hougaard, David M ; Børglum, Anders ; Werge, Thomas ; Nordentoft, Merete. / No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder. I: Psychological Medicine. 2021 ; Bind 51, Nr. 3. s. 479-484.

Bibtex

@article{b66c3d9a1e7a48e6889503f1b0377786,
title = "No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder",
abstract = "BACKGROUND: Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.METHODS: We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.RESULTS: The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95-1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72-3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08-1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27-3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36-5.53), the inclusion of various PRS did not appreciably alter this association.CONCLUSION: The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.",
keywords = "Cannabis, genetics, pleiotropy, polygenic risk, schizophrenia",
author = "Carsten Hjorth{\o}j and Uddin, {Md Jamal} and Theresa Wimberley and S{\o}ren Dalsgaard and Hougaard, {David M} and Anders B{\o}rglum and Thomas Werge and Merete Nordentoft",
year = "2021",
month = feb,
doi = "10.1017/S0033291719003362",
language = "English",
volume = "51",
pages = "479--484",
journal = "Psychological Medicine",
issn = "0033-2917",
publisher = "Cambridge University Press",
number = "3",

}

RIS

TY - JOUR

T1 - No evidence of associations between genetic liability for schizophrenia and development of cannabis use disorder

AU - Hjorthøj, Carsten

AU - Uddin, Md Jamal

AU - Wimberley, Theresa

AU - Dalsgaard, Søren

AU - Hougaard, David M

AU - Børglum, Anders

AU - Werge, Thomas

AU - Nordentoft, Merete

PY - 2021/2

Y1 - 2021/2

N2 - BACKGROUND: Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.METHODS: We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.RESULTS: The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95-1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72-3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08-1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27-3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36-5.53), the inclusion of various PRS did not appreciably alter this association.CONCLUSION: The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.

AB - BACKGROUND: Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.METHODS: We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.RESULTS: The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95-1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72-3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08-1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27-3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36-5.53), the inclusion of various PRS did not appreciably alter this association.CONCLUSION: The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.

KW - Cannabis

KW - genetics

KW - pleiotropy

KW - polygenic risk

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85076280451&partnerID=8YFLogxK

U2 - 10.1017/S0033291719003362

DO - 10.1017/S0033291719003362

M3 - Journal article

C2 - 31813396

VL - 51

SP - 479

EP - 484

JO - Psychological Medicine

JF - Psychological Medicine

SN - 0033-2917

IS - 3

ER -