Single nucleotide polymorphism analysis in panic disorder candidate genes: Neuropeptide Y and the neuropeptide Y-Y1 receptor

Using a high throughput method for genotyping SNPs based on a single base extension reaction, we have employed a family-based design to investigate the role of the genes for Neuropeptide Y (NPY) and the Y1 Neuropeptide Y receptor (NPY1R) in the development of panic disorder. We have genotyped 613 individuals in 70 pedigrees, as well as 83 triads. Subjects were genotyped at 1) 6 informative single nucleotide polymorphisms (SNPs) in the region of NPY; 2) 1 informative single nucleotide polymorphism in the region of NPY1R, and the data are currently being analyzed for genetic association and linkage. In addition to standard linkage (using recessive/dominant genetic models, three diagnostic models, and tests of heterogeneity) and family-based association tests (TDT and HRR), we plan to analyze the data using TRANSMIT, a program that compares the transmission of multilocus haplotypes from parents to affected offspring. Its main advantage is its ability to handle missing parental genotypes or phase-unknown parental genotypes. This work highlights the utility of exploiting SNP information from the Human Genome Project, particularly with regard to the use of multilocus haplotypes in the search for disease susceptibility loci.