Assuming biological pleiotropy to be the underlying mechanism, we devised a test to discover the variants shared between ND and schizophrenia. Using this approach, we identified multiple genes associated with both conditions (Table 3). Of these genes, the CHRNA5-CHRNA3-CHRNB4 cluster had been found to be associated with CPD23 and other ND related traits, and it was reported to be associated with schizophrenia in the latest schizophrenia GWAS meta-analysis from PGC1. Several of the genes had been reported to be associated with schizophrenia (HLA-B and MAD1L1)28 and epilepsy (KCNT1, PRICKLE2 and RBFOX1)353637, suggesting that they might play a role in smoking behaviors as well. Our analyses also identified some novel genes shared between schizophrenia and ND, including a group of long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558, RBFOX1 and TINCR), a group of post-translation modification genes (MANBA, UBE2D3, and RANGAP1) and a group of energy production genes (XYLB, MTRF1 and ENOX1). Long non-coding RNAs were suggested to play a role in schizophrenia3839, the identification of multiple long non-coding RNAs was intriguing.
