Family Genomics of Bipolar Disorder

This study examined the segregation of variants with phenotype in pedigrees harboring bipolar disorder.]]>
We chose a subset of individuals within each pedigree so as to maximize power under the most likely inheritance mode, as follows: (i) We sequenced a single affected individual and a single unaffected individual from pedigrees with a suggestive per-pedigree linkage peak and predicted dominant inheritance. (ii) We sequenced a parent-child trio or quartet from pedigrees with a single, suggestive per-pedigree linkage peak and either dominant or recessive inheritance. In pedigrees for which polygenic inheritance was more likely, we sequenced either (iii) a subset of affected individuals and 0-1 unaffected individuals or (iv) all available individuals.]]>
The bipolar disorder pedigrees sequenced in this study were drawn from a set of 972 multiply affected pedigrees collected by the NIMH Genetics Initiative and by sites at the University of California, San Diego, the University of California, San Francisco, and the University of Chicago. This sample has been described in Badner JA, et al. (2012) Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms. Mol Psychiatry 17(8):818-826. DNA derived from whole blood or from lymphoblastoid cell lines was obtained from the Rutgers University Cell and DNA Repository and from the Corriell Institute. We selected pedigrees and individuals for sequencing by considering family structure, per-pedigree LOD scores at 4,500 genome-wide SNPs, and the polygenic risk score in each pedigree's proband: Smith EN, et al. (2009) Genome-wide association study of bipolar disorder in European American and African American individuals. Mol Psychiatry 14(8):755-763.]]>