Genetic correlation between smoking behaviors and schizophrenia

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.