Phenotype comorbidity is common in complex diseases and traits78. Pleiotropy, or shared genetic liability, may be an underlying mechanism of these comorbidities. Under this condition, different approaches have been developed to identify genes shared by the comorbid conditions4041, and these approaches seem more powerful than standard GWAS842. Another advantage of these methods is that they can use the large number of GWAS datasets produced by a single phenotype/trait analyses. The approach we used to identify these shared loci is conservative. In our analyses, we excluded all markers reaching genome-wide significance from both schizophrenia and smoking traits and required a balanced contribution from both traits. Under this condition, if a marker reached genome wide significance for schizophrenia but had a modest association with ND traits (say P-values between 10−4 to 5 × 10−6), it was excluded from our joint testing. Similarly, some markers would be excluded if they reached genome wide significance in ND traits. Because the GWASs used have different sample sizes, and therefore varied in their statistical power, it is inevitable that we would miss some markers from the more powerful GWAS when we required balanced summary statistics in the joint testing.
