Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium

Roseann E Peterson; Tim B Bigdeli; Stephan Ripke; Silviu-Alin Bacanu; Pablo V Gejman; Douglas F Levinson; Qingqin S Li; Dan Rujescu; Marcella Rietschel; Daniel R Weinberger; Richard E Straub; James T R Walters; Michael J Owen; Michael C O'Donovan; Bryan J Mowry; Roel A Ophoff; Ole A Andreassen; Tõnu Esko; Tracey L Petryshen; Kenneth S Kendler; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Ayman H Fanous

doi:10.1016/j.jpsychires.2021.02.027

Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium

J Psychiatr Res. 2021 May:137:215-224. doi: 10.1016/j.jpsychires.2021.02.027. Epub 2021 Feb 18.

Authors

Roseann E Peterson¹, Tim B Bigdeli², Stephan Ripke³, Silviu-Alin Bacanu⁴, Pablo V Gejman⁵, Douglas F Levinson⁶, Qingqin S Li⁷, Dan Rujescu⁸, Marcella Rietschel⁹, Daniel R Weinberger¹⁰, Richard E Straub¹¹, James T R Walters¹², Michael J Owen¹², Michael C O'Donovan¹², Bryan J Mowry¹³, Roel A Ophoff¹⁴, Ole A Andreassen¹⁵, Tõnu Esko¹⁶, Tracey L Petryshen¹⁷, Kenneth S Kendler⁴; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Ayman H Fanous¹⁸

Affiliations

¹ Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. Electronic address: peterson.roseann@gmail.com.
² Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
³ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA; Dept. of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin 10117, Germany.
⁴ Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
⁵ Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
⁶ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁷ Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Raritan, NJ, USA.
⁸ Department of Psychiatry, University of Halle, Halle, Germany; Department of Psychiatry, University of Munich, Munich, Germany.
⁹ Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
¹⁰ Lieber Institute for Brain Development, Baltimore, MD, USA; Departments of Psychiatry, Neurology, Neuroscience and Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹¹ Lieber Institute for Brain Development, Baltimore, MD, USA.
¹² MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.
¹³ Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia; Queensland Centre for Mental Health Research, University of Queensland, Brisbane, Queensland, Australia.
¹⁴ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands.
¹⁵ NORMENT Centre and KG Jebsen Centre for Neurodevelopmental disorders, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁶ Estonian Genome Center, University of Tartu, Tartu, Estonia; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁷ Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Boston, MA, USA.
¹⁸ Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA; VA New York Harbor Healthcare System, Brooklyn, NY, USA. Electronic address: Ayman.Fanous@downstate.edu.

Abstract

While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (r_g = 0.159; P = 5.05 × 10^-10), cigarettes-smoked-per-day (r_g = 0.094; P = 0.006), and age-of-onset of smoking (r_g = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (r_g = 0.624, P = 0.002) and cigarettes-smoked-per-day (r_g = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10^-5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10^-8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.

Keywords: Cigarettes per day; GWAS; Genetics; Pleiotropy; Schizophrenia; Smoking initiation.

Published by Elsevier Ltd.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study*
Genomics
Humans
Membrane Proteins / genetics
Nerve Tissue Proteins
Phenotype
Polymorphism, Single Nucleotide / genetics
Schizophrenia* / epidemiology
Schizophrenia* / genetics
Smoking / genetics

Substances

Membrane Proteins
Nerve Tissue Proteins
TMEM106B protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding