Fast Genome-Wide QTL Analysis Using Mendel

Abstract: Pedigree GWAS (Option 29) in the current version of the Mendel software is an optimized subroutine for performing large scale genome-wide QTL analysis. This analysis (a) works for random sample data, pedigree data, or a mix of both, (b) is highly efficient in both run time and memory requirement, (c) accommodates both univariate and multivariate traits, (d) works for autosomal and x-linked loci, (e) correctly deals with missing data in traits, covariates, and genotypes, (f) allows for covariate adjustment and constraints among parameters, (g) uses either theoretical or SNP-based empirical kinship matrix for additive polygenic effects, (h) allows extra variance components such as dominant polygenic effects and household effects, (i) detects and reports outlier individuals and pedigrees, and (j) allows for robust estimation via the $t$-distribution. The current paper assesses these capabilities on the genetics analysis workshop 19 (GAW19) sequencing data. We analyzed simulated and real phenotypes for both family and random sample data sets. For instance, when jointly testing the 8 longitudinally measured systolic blood pressure (SBP) and diastolic blood pressure (DBP) traits, it takes Mendel 78 minutes on a standard laptop computer to read, quality check, and analyze a data set with 849 individuals and 8.3 million SNPs. Genome-wide eQTL analysis of 20,643 expression traits on 641 individuals with 8.3 million SNPs takes 30 hours using 20 parallel runs on a cluster. Mendel is freely available at \url{http://www.genetics.ucla.edu/software}.