Bipolar Disorder Candidate Gene Custom SNP panel: Design and Preliminary Results

Burmeister Margit; Scott Laura J.; Li Yun; Thompson Robert C.; Li Jun; Meng Fan; Guan Weihua; Absher Devin; Vawter Marquis P.; Choudary Prabhakara; Tomita Hiroaki; Evans Simon J.; Bunney William E,; Jones Edward G.; Barchas Jack D.; Akil Huda; Watson Stanley J.; Myers Richard M.; Boehnke Michael;
World Congress of Psychiatric Genetics. 2006.

Abstract

We designed a Bipolar Disorder candidate gene panel for the 1536 SNP Illumina Golden Gate assay. Inclusion criteria were association with Bipolar Disorder in 1 large study or >2 smaller studies, reproducible or RT-PCR confirmed difference in express ion between bipolar disorder and controls in microarray studies from brain mRNA, strong evidence of biological implication or mouse model with relevant phenotypes. Genes were defined as all exons and introns, plus 10 kb 5¿ to the start of transcri ption and 5 kb 3¿ to the last base of the longest transcript. HapMap II SNPs with minor allele frequency > 0.05 were identified for all SNPs in > 120 genes. After eliminating SNPs with an Illumina design score <0.6, optimal SNPs were chosen to cove r all HAPMAP bins and singletons by at least 1 SNP within LD of r2 >0.8. All nonsynonymous SNPs were added regardless of MAF and HapMap. Some large genes with > 100 HapMap SNPs had to be excluded for efficiency, as were genes without HapMap SNPs, us ually due to genome map uncertainty. The final list includes 96 genes, with a median of 10 SNPs per gene (average 16; range 0 to 176). We will present preliminary results using this panel in an association study of 476 cases and 470 controls fro m the NIMH genetic initiative.