Analysis of ANK3 and CACNA1C variants identified in bipolar disorder whole genome sequence data

Genetic markers in the genes encoding ankyrin 3 (ANK3) and the α-calcium channel subunit (CACNA1C) are associated with bipolar disorder (BP). The associated variants in the CACNA1C gene are mainly within intron 3 of the gene. ANK3 BP-associated variants are in two distinct clusters at the ends of the gene, indicating disease allele heterogeneity

A quick and simple method for detecting subjects with abnormal genetic background in case-control samples

It is important that case-control samples be drawn from a genetically homogeneous population in order to avoid artefactual false positive results and to enhance power to detect disease mutations and markers in linkage disequilibrium with them. Tests which simply compare overall marker allele frequencies between cases and controls will fail to identify a relatively small number of subjects drawn from a different genetic background who could usefully be discarded from the sample. Such subjects can be identified using multilocus tests, but previously described tests have been unnecessarily complex and cumbersome for this simple application. We describe a straightforward test, implemented in the CHECKHET program, which uses a measure of genetic difference and permutation procedures to rapidly identify such subjects using genotypes from multiple unlinked markers. It seems to perform reasonably well on simulated data, and with real data appears to identify two abnormal subjects within a case-control sample. We recommend that such tests be routinely applied to case-control samples once sufficient numbers of markers have been genotyped within them.link_to_subscribed_fulltex