A Single Nucleotide Polymorphism Fine Mapping Study of Chromosome 1q42.1 Reveals the Vulnerability Genes for Schizophrenia, GNPAT and DISC1: Association with Impairment of Sustained Attention

The marker D1S251 of chromosome 1q42.1 showed significant association with schizophrenia in a Taiwanese sample. We used single nucleotide polymorphism (SNP) fine mapping to search for the vulnerability genes of schizophrenia. We selected 120 SNPs covering 1 Mb around D1S251 from the public database. These selected SNPs were initially validated if allele frequency was >10%. Forty-seven validated SNPs were genotyped in 102 families with at least 2 siblings affected with schizophrenia. Two SNP blocks showed significant association with schizophrenia. Block 1 (five-SNP), located between intron 2 and intron 13 of the glyceronephosphate O-acyltransferase ( GNPAT) gene, showed the most significant associations using single-locus TDT ( z = −2.07, p = .038, df = 1) and haplotype association analyses ( z = −1.99, p = .046, df = 1). Block 2 (two-SNP), located between intron 4 and intron 5 of the disrupted-in-schizophrenia 1 ( DISC1) gene, also showed the most significant results in both the single-locus ( z = −3.22, p = .0013, df = 1) and haplotype association analyses ( z = 3.35, p = .0008, df = 1). The association of the DISC1 gene with schizophrenia was mainly in the patient group with sustained attention deficits as assessed by the Continuous Performance Test. Chromosome 1q42.1 harbors GNPAT and DISC1 as candidate genes for schizophrenia, and DISC1 is associated with sustained attention deficits.