A statistical framework for expression quantitative trait loci mapping

被引:16
作者
Chen, Meng
Kendziorski, Christina
机构
[1] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA
[2] Pfizer Global Res & Dev, Groton, CT 06940 USA
关键词
D O I
10.1534/genetics.107.071407
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In 2001, Sen and Churchill reported a general Bayesian framework for quantitative trait loci (QTL) mapping in inbred line crosses. The framework is a powerful one, as many QTL mapping methods can be represented as special cases and many important considerations are accommodated. These considerations include accounting for covariates, nonstandard crosses, missing genotypes, genotyping errors, multiple interacting QTL, and nonnormal as well as multivariate phenotypes. The dimension of a multivariate phenotype easily handled within the Framework is bounded by the number of subjects, as a full-rank covariance matrix describing correlations across the phenotypes is required. We address this limitation and extend the Sen-Churchill framework to accommodate expression quantitative trait loci (eQTL) mapping studies, where high-dimensional gene-expression phenotypes are obtained via microarrays. Doing so allows for the precise comparison of existing eQTL mapping approaches and facilitates the development of an eQTL interval-mapping approach that shares information across transcripts and improves localization of eQTL. Evaluations are based on simulation studies and a study of diabetes in mice.
引用
收藏
页码:761 / 771
页数:11
相关论文
共 34 条
  • [1] PGC-1α at the crossroads of type 2 diabetes
    Attie, AD
    Kendziorski, CM
    [J]. NATURE GENETICS, 2003, 34 (03) : 244 - 245
  • [2] BARRETT T, 2007, NUCLEIC ACIDS RES, V33, pD562
  • [3] Genetic dissection of transcriptional regulation in budding yeast
    Brem, RB
    Yvert, G
    Clinton, R
    Kruglyak, L
    [J]. SCIENCE, 2002, 296 (5568) : 752 - 755
  • [4] R/qtl: QTL mapping in experimental crosses
    Broman, KW
    Wu, H
    Sen, S
    Churchill, GA
    [J]. BIOINFORMATICS, 2003, 19 (07) : 889 - 890
  • [5] CHEN M, 2006, THESIS U WISCONSIN M
  • [6] Human genetics - An expression of interest
    Cox, NJ
    [J]. NATURE, 2004, 430 (7001) : 733 - 734
  • [7] Improved statistical tests for differential gene expression by shrinking variance components estimates
    Cui, XG
    Hwang, JTG
    Qiu, J
    Blades, NJ
    Churchill, GA
    [J]. BIOSTATISTICS, 2005, 6 (01) : 59 - 75
  • [8] Dupuis J, 1999, GENETICS, V151, P373
  • [9] GELFOND J, 2006, BIOMETRICS, V62, P19
  • [10] Gentleman R, 2004, COMPSTAT 2004: PROCEEDINGS IN COMPUTATIONAL STATISTICS, P171