PT  - JOURNAL ARTICLE
AU  - Andrey Ziyatdinov
AU  - Miquel Vázquez-Santiago
AU  - Helena Brunel
AU  - Angel Martinez-Perez
AU  - Hugues Aschard
AU  - Jose Manuel Soria
TI  - lme4qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals
AID  - 10.1101/139816
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 139816
4099  - http://biorxiv.org/content/early/2017/05/18/139816.short
4100  - http://biorxiv.org/content/early/2017/05/18/139816.full
AB  - Summary Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated ob- servations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential in advanced QTL models. Apart from applications in linkage studies of related individuals, such functionalities are of high interest for association studies in situations where multiple covariance matrices need to be modeled, a scenario not covered by many genome-wide association study (GWAS) software.To address the aforementioned limitations, we developed a new R package lme4qtl as an extension of lme4. First, lme4qtl contributes new models for genetic studies within a single tool integrated with lme4 and its companion packages. Second, lme4qtl offers a flexible framework for scenarios with multiple levels of relatedness and becomes efficient when covariance matrices are sparse. We showed the value of our pack- age using real family-based data in the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2) project.Availability and implementation lme4qtl is available at https://github.com/variani/lme4qtl.Contact ziyatdinov{at}hsph.harvard.edu