The feasibility of oligogenic combined segregation and linkage analysis in CEPH pedigrees

The CEPH samples are an invaluable resource for mapping genes that contribute to traits that can be measured in cell lines. With the many markers that have already been genotyped for the Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees and are readily available, one need only obtain phenotypes to conduct a linkage analysis. For Genetic Analysis Workshop 15 (GAW15), over 3000 expression levels of genes in lymphoblastoid cells in 14 of the CEPH pedigrees were provided. For this study, eight of these expression levels were selected to obtain a spectrum of heritabilities, three were selected based on linkage results with traditional LOD scores >3, and one trait was selected at random. A Bayesian Monte Carlo Markov chain oligogenic segregation and linkage analysis was conducted on each of these 12 traits using the genome-wide single-nucleotide polymorphism linkage markers provided for GAW15. Our goal was to assess the ability of these methods to map genes in the CEPH pedigrees. Surprisingly, positive linkage signals were found for all 12 traits, even those with a very small traditionally calculated heritability. However, the portion of the variance attributed to genetic sources by the oligogenic segregation analysis differed substantially in some cases from the traditional heritability. It appears that genetic variance estimated from oligogenic segregation analysis may be a better indicator of whether genes can be mapped for complex traits than traditional heritability.