title: Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction.
abstract: We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in-patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10-50-1.4 × 10-6) and BPD (P = 1.7 × 10-9-1.9 × 10-3), showing shared genetic etiology between psychosis and addiction. Using standardized scores for SCZ and BPD scaled to a unit increase doubling the risk of the corresponding disorder, the odds ratios for alcohol and substance use disorders range from 1.19 to 1.31 for the SCZ-PRS, and from 1.07 to 1.29 for the BPD-PRS. Furthermore, we show that as regular smoking becomes more stigmatized and less prevalent, these biological risk factors gain importance as determinants of the behavior.
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Gunnar W
authors.initials: GW
authors.lastname: Reginsson
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Andres
authors.initials: A
authors.lastname: Ingason
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.|MRC Integrative Epidemiology Unit, Oakfield House, Oakfield Grove, University of Bristol, BS8 2EG, UK.
authors.forename: Jack
authors.initials: J
authors.lastname: Euesden
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Gyda
authors.initials: G
authors.lastname: Bjornsdottir
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Sigurgeir
authors.initials: S
authors.lastname: Olafsson
authors.affiliation: Department of Psychiatry, Landspitalinn University Hospital, Iceland.
authors.forename: Engilbert
authors.initials: E
authors.lastname: Sigurdsson
authors.affiliation: Humus, Reykjavik, Iceland.
authors.forename: Hogni
authors.initials: H
authors.lastname: Oskarsson
authors.affiliation: SAA-National Center of Addiction Medicine, Iceland.
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Tyrfingsson
authors.affiliation: SAA-National Center of Addiction Medicine, Iceland.
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Runarsdottir
authors.affiliation: SAA-National Center of Addiction Medicine, Iceland.|Faculty of Psychology, University of Iceland, Iceland.
authors.forename: Ingunn
authors.initials: I
authors.lastname: Hansdottir
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Stacy
authors.initials: S
authors.lastname: Steinberg
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.affiliation: deCODE genetics/Amgen, Iceland.|Department of Engineering and Natural Sciences, University of Iceland, Iceland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: deCODE genetics/Amgen, Iceland.
authors.forename: Thorgeir E
authors.identifier: 0000-0002-5149-7040
authors.initials: TE
authors.lastname: Thorgeirsson
authors.affiliation: deCODE genetics/Amgen, Iceland.|Faculty of Medicine, University of Iceland, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics*; D000073865:Cigarette Smoking / Q000235:genetics*; D005260:Female; D006801:Humans; D007055:Iceland; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D016017:Odds Ratio; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*; D019966:Substance-Related Disorders / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*
keywords: polygenic scores; psychotic disorders; substance abuse