Genetic correlation between smoking behaviors and schizophrenia

Sarah M. Hartz, Amy C. Horton, Dana B. Hancock, Timothy B. Baker, Neil E. Caporaso, Li Shiun Chen, John E. Hokanson, Sharon M. Lutz, Mary L. Marazita, Daniel W. McNeil, Carlos N. Pato, Michele T. Pato, Eric O. Johnson, Laura J. Bierut

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40 Scopus citations


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 (h2 g) of each of the smoking phenotypes was computed using LD score regression (ever/never smoker h2 g = 0.08, age of onset of smoking h2 g = 0.06, CPD h2 g = 0.06, nicotine dependence h2 g = 0.15, current/former smoker h2 g = 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.

Original languageEnglish
Pages (from-to)86-90
Number of pages5
JournalSchizophrenia research
StatePublished - Apr 2018


  • Genetic correlation
  • Nicotine dependence
  • Schizophrenia


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