title: Genetic correlation between smoking behaviors and schizophrenia.
abstract: Nicotine dependence is highly comorbid with schizophrenia, and the etiology of the comorbidity is unknown. To determine whether there is a genetic correlation of smoking behavior with schizophrenia, genome-wide association study (GWAS) meta-analysis results from five smoking phenotypes (ever/never smoker (N=74,035), age of onset of smoking (N=28,647), cigarettes smoked per day (CPD, N=38,860), nicotine dependence (N=10,666), and current/former smoker (N=40,562)) were compared to GWAS meta-analysis results from schizophrenia (N=79,845) using linkage disequilibrium (LD) score regression. First, the SNP heritability (h2g) of each of the smoking phenotypes was computed using LD score regression (ever/never smoker h2g=0.08, age of onset of smoking h2g=0.06, CPD h2g=0.06, nicotine dependence h2g=0.15, current/former smoker h2g=0.07, p<0.001 for all phenotypes). The SNP heritability for nicotine dependence was statistically higher than the SNP heritability for the other smoking phenotypes (p<0.0005 for all two-way comparisons). Next, a statistically significant (p<0.05) genetic correlation was observed between schizophrenia and three of the five smoking phenotypes (nicotine dependence rg=0.14, CPD rg=0.12, and ever/never smoking rg=0.10). These results suggest that there is a component of common genetic variation that is shared between smoking behaviors and schizophrenia.
authors.affiliation: Washington University School of Medicine in St. Louis, United States. Electronic address: hartzs@wustl.edu.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Hartz
authors.affiliation: Washington University School of Medicine in St. Louis, United States.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Horton
authors.affiliation: RTI International, United States.
authors.forename: Dana B
authors.initials: DB
authors.lastname: Hancock
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, United States.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Baker
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, United States.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Washington University School of Medicine in St. Louis, United States.
authors.forename: Li-Shiun
authors.initials: LS
authors.lastname: Chen
authors.affiliation: University of Colorado, Anschutz Medical Campus, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.affiliation: University of Colorado, Anschutz Medical Campus, United States.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Lutz
authors.affiliation: Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine; Department of Human Genetics, Graduate School of Public Health; University of Pittsburgh, Pittsburgh, PA, United States.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.affiliation: West Virginia University, United States.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: McNeil
authors.affiliation: SUNY Downstate Medical Center, United States.
authors.forename: Carlos N
authors.initials: CN
authors.lastname: Pato
authors.affiliation: SUNY Downstate Medical Center, United States.
authors.forename: Michele T
authors.initials: MT
authors.lastname: Pato
authors.affiliation: RTI International, United States.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Johnson
authors.affiliation: Washington University School of Medicine in St. Louis, United States.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
mesh_terms: D015897:Comorbidity; D020022:Genetic Predisposition to Disease; D006801:Humans; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics*; D012907:Smoking / Q000235:genetics*
keywords: Genetic correlation; Nicotine dependence; Schizophrenia