Referenced in: none

Automatically associated channels: Cavγ2

Title: Evidence for association of bipolar disorder to haplotypes in the 22q12.3 region near the genes stargazin, IFT27 and parvalbumin.

Authors: Stephanie Nissen, Sherri Liang, Tatyana Shehktman, John R Kelsoe, , Tiffany A Greenwood, Caroline M Nievergelt, Rebecca McKinney, Paul D Shilling, Erin N Smith, Nicholas J Schork, Cinnamon S Bloss, John I Nurnberger, Howard J Edenberg, Tatiana Foroud, Daniel L Koller, Elliot S Gershon, Chunyu Liu, Judith A Badner, William A Scheftner, William B Lawson, Evaristus A Nwulia, Maria Hipolito, William Coryell, John Rice, William Byerley, Francis J McMahon, Wade H Berrettini, James B Potash, Peter P Zandi, Pamela B Mahon, Melvin G McInnis, Sebastian Zöllner, Peng Zhang, David W Craig, Szabolics Szelinger, Thomas B Barrett, Thomas G Schulze

Journal, date & volume: Am. J. Med. Genet. B Neuropsychiatr. Genet., 2012 Dec , 159B, 941-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23038240

Abstract
We have previously reported genome-wide significant linkage of bipolar disorder to a region on 22q12.3 near the marker D22S278. Towards identifying the susceptibility gene, we have conducted a fine-mapping association study of the region in two independent family samples, an independent case-control sample and a genome-wide association dataset. Two hundred SNPs were first examined in a 5 Mb region surrounding the D22S278 marker in a sample of 169 families and analyzed using PLINK. The peak of association was a haplotype near the genes stargazin (CACNG2), intraflagellar transport protein homolog 27 (IFT27) and parvalbumin (PVALB; P = 4.69 × 10(-4)). This peak overlapped a significant haplotype in a family based association study of a second independent sample of 294 families (P = 1.42 × 10(-5)). Analysis of the combined family sample yielded statistically significant evidence of association to a rare three SNP haplotype in the gene IFT27 (P = 8.89 × 10(-6)). Twelve SNPs comprising these haplotypes were genotyped in an independent sample of 574 bipolar I cases and 550 controls. Statistically significant association was found for a haplotype window that overlapped the region from the first two family samples (P = 3.43 × 10(-4)). However, analyses of the two family samples using the program LAMP, found no evidence for association in this region, but did yield significant evidence for association to a haplotype 3' of CACNG2 (P = 1.76 × 10(-6)). Furthermore, no evidence for association was found in a large genome-wide association dataset. The replication of association to overlapping haplotypes in three independent datasets suggests the presence of a bipolar disorder susceptibility gene in this region.