A recent surge of evidence implicating myelin abnormalities in the etiology of schizophrenia has been found. This study is a family-based genetic association analysis examining the myelin-associated glycoprotein (MAG) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) genes in schizophrenia. About 246 families of primarily European-Caucasian origin were genotyped for MAG rs2301600, rs720308, rs720309, rs756796, and CNP rs2070106 single nucleotide polymorphisms (SNPs). The FBAT program (v1.7.2) and Transmit were used to analyze individual SNPs and haplotypes, respectively. The CNP SNP (rs2070106) was potentially associated with schizophrenia (P=0.027). MAG variants were not associated with disease transmission based on single marker or haplotype analysis. A significant maternal parent-of-origin effect for the CNP risk allele for schizophrenia was found (P=0.003). No CNP-MAG gene-gene interaction conferred increased risk for schizophrenia. Our finding provides support for potential association of the CNP gene but not the MAG gene in schizophrenia in a Caucasian population.