Year: 2014
Type: article
Abstract: We propose a novel variance component approach for the analysis of next-generation sequencing data. Our method is based on the detection of the proportion of the trait phenotypic variance that can be explained by the introduction of a new variance component that accounts for the local gene-specific departure of the empirical kinship relationship matrix, estimated from single-nucleotide polymorphism (SNP) genotypes, from their theoretical expectation based on the genealogical information in the pedigree. We tested our method with simulated phenotypes and imputed SNP genotypes from the Genetic Analysis Workshop 18 data set. We observed considerable variation in the differences between theoretical and gene-specific kinship estimates that proved to be informative for our test and allowed us to detect the MAP4 causal gene at a genome-wide significance level. The distribution of our test statistic show no inflation under the null hypothesis and results from a random set of genes suggest that the detection of MAP4 is both sensitive and specific. The use of 2 different strategies for the selection of the SNPs used to derive the gene-specific empirical kinship relationship matrices provides us with suggestive evidence that our method is performing as an empirical test of linkage.
Source: BMC Proceedings
Institution: Texas Biomedical Research Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,290
Funders: Texas Biomedical Research Institute, Sir Bobby Charlton Foundation, National Institutes of Health, National Institute of Mental Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: Multiethnic Study of Type 2 Diabetes Genes, Identifying T2D Variants by DNA Sequencing in Multiethnic Samples, G1700758416, Identification and Replication of Type 2 Diabetes Genes in Mexican Americans, Discovery of Functional Variants in Type 2 Diabetes Genes in Mexican Americans, Identifying variants causal for Type 2 Diabetes in Major human populations, NIDDM Susceptibility Genes in Mexican Americans, Genetics of Gallbladder Disease in Mexican Americans, Solar-Eclipse Computational Tools for Imaging Genetics, G725404114, Genetic Analysis of Common Diseases: An Evaluation, G9000110552
OpenAlex ID: W2013974354