Genetic association studies have implicated the TSNAX/DISC1 (disrupted in schizophrenia 1) in schizophrenia (SCZ), bipolar affective disorder (BPAD) and major depression. This study was performed to assess the possible involvement of TSNAX/DISC1 locus in the aetiology of BPAD and SCZ in the Southern Indian population. We genotyped seven single nucleotide polymorphism (SNPs) from TSNAX/DISC1 region in 1252 individuals (419 BPAD patients, 408 SCZ patients and 425 controls). Binary logistic regression revealed a nominal association for rs821616 in DISC1 for BPAD and also combined cases of BPAD or SCZ, but after correcting for multiple testing, these results were non-significant. However, significant association was observed with BPAD, as well as combined cases of BPAD or SCZ, within the female subjects for the rs766288 after applying false discovery rate corrections at the 0.05 level. Two-locus analysis showed C-C (rs766288-rs2812393) as a risk combination in BPAD, and G-T (rs2812393-rs821616) as a protective combination in SCZ and combined cases of BPAD or SCZ. Female-specific associations were observed for rs766288-rs2812393, rs766288-rs821616 and rs8212393-rs821616 in two-locus analysis. Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD. INTRODUCTION Schizophrenia (SCZ) and bipolar affective disorder (BPAD) are severe psychiatric disorders, each affecting approximately 1% of the population worldwide. 1 Family, twin and adoption studies confirm that genetic factors have a significant role in the aetiology of these disorders. 2 Several putative susceptibility loci and genes have been implicated, of which the TSNAX/DISC1 locus has shown encouraging results. The gene disrupted in schizophrenia 1 (DISC1) was first identified in a large Scottish family with a balanced translocation t (1, 11) (q42.2, q14.3) segregating with major mental illness, including SCZ, BPAD and recurrent major depression. [3][4][5] The translinassociated factor X (TRAX; TSNAX) gene is located adjacent to the DISC1 towards the 5 0 region. Subsequently several linkage studies have observed linkage near 1q42, which harbours DISC1, to SCZ 6-9 and BPAD. 10-12 Several population-based and family-based association studies have supported the role of the TSNAX/DISC1 locus in SCZ and/or BPAD in Caucasian 13-25 and Asian 26-28 populations. However, other studies have failed to replicate association between TSNAX/DISC1