title: Dissecting high-dimensional phenotypes with bayesian sparse factor analysis of genetic covariance matrices.
abstract: Quantitative genetic studies that model complex, multivariate phenotypes are important for both evolutionary prediction and artificial selection. For example, changes in gene expression can provide insight into developmental and physiological mechanisms that link genotype and phenotype. However, classical analytical techniques are poorly suited to quantitative genetic studies of gene expression where the number of traits assayed per individual can reach many thousand. Here, we derive a Bayesian genetic sparse factor model for estimating the genetic covariance matrix (G-matrix) of high-dimensional traits, such as gene expression, in a mixed-effects model. The key idea of our model is that we need consider only G-matrices that are biologically plausible. An organism's entire phenotype is the result of processes that are modular and have limited complexity. This implies that the G-matrix will be highly structured. In particular, we assume that a limited number of intermediate traits (or factors, e.g., variations in development or physiology) control the variation in the high-dimensional phenotype, and that each of these intermediate traits is sparse - affecting only a few observed traits. The advantages of this approach are twofold. First, sparse factors are interpretable and provide biological insight into mechanisms underlying the genetic architecture. Second, enforcing sparsity helps prevent sampling errors from swamping out the true signal in high-dimensional data. We demonstrate the advantages of our model on simulated data and in an analysis of a published Drosophila melanogaster gene expression data set.
authors: Department of Biology, Duke University, Durham, North Carolina 27708, USA. daniel.e.runcie@gmail.com
authors: Daniel E
authors: DE
authors: Runcie
authors: Sayan
authors: S
authors: Mukherjee
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D005075:Biological Evolution; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D008962:Models, Theoretical; D010641:Phenotype
keywords: Bayesian inference; G matrix; animal model; factor model; sparsity
references: Genetics. 2006 Jun;173(2):1135-44
references: 16547106
references: Nat Protoc. 2009;4(1):44-57
references: 19131956
references: Genetica. 2009 Jun;136(2):271-84
references: 18695991
references: Am Nat. 2004 Mar;163(3):329-40
references: 15026971
references: J Math Biol. 1989;27(4):429-50
references: 2769086
references: Evolution. 2005 May;59(5):1027-38
references: 16136802
references: PLoS Genet. 2010 Sep 16;6(9):e1001117
references: 20862358
references: Evolution. 1996 Jun;50(3):967-976
references: 28565291
references: Genome Res. 2012 Feb;22(2):386-97
references: 21940837
references: Trends Genet. 2005 Nov;21(11):616-23
references: 16154229
references: PLoS Genet. 2009 May;5(5):e1000479
references: 19424432
references: J Dairy Sci. 2002 Apr;85(4):968-75
references: 12018443
references: Nat Genet. 2009 Mar;41(3):299-307
references: 19234471
references: Genet Epidemiol. 2010 Apr;34(3):222-231
references: 20013942
references: Am J Hum Genet. 2010 Jan;86(1):6-22
references: 20074509
references: Evolution. 1992 Jun;46(3):616-626
references: 28568666
references: Genetics. 1957 Jul;42(4):524-30
references: 17247713
references: PLoS Comput Biol. 2010 May 06;6(5):e1000770
references: 20463871
references: Philos Trans R Soc Lond B Biol Sci. 2004 Jun 29;359(1446):873-90
references: 15306404
references: Genetics. 2008 Oct;180(2):1153-66
references: 18757923
references: J Am Stat Assoc. 2008 Dec 1;103(484):1438-1456
references: 21218139
references: Nat Genet. 2012 Jun 17;44(7):821-4
references: 22706312
references: Evolution. 1996 Oct;50(5):1766-1774
references: 28565589
references: Genetics. 1999 Oct;153(2):825-35
references: 10610347
references: Evolution. 1979 Mar;33(1Part2):402-416
references: 28568194
references: Genet Sel Evol. 2007 Sep-Oct;39(5):481-94
references: 17897592
references: Evolution. 2011 Nov;65(11):3126-37
references: 22023580
references: Genet Sel Evol. 2009 Jan 30;41:21
references: 19284520
references: Genetics. 2004 Dec;168(4):2295-306
references: 15611193
references: Evolution. 1979 Mar;33(1Part2):371-380
references: 28568191
references: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20063-6
references: 19104053
references: Nucleic Acids Res. 2009 Jan;37(1):1-13
references: 19033363
references: J Evol Biol. 2008 Sep;21(5):1201-19
references: 18662244
references: PLoS Genet. 2011 Jan 20;7(1):e1001276
references: 21283789
references: Biometrika. 2011 Jun;98(2):291-306
references: 23049129
references: Proc Natl Acad Sci U S A. 2010 Jan 26;107 Suppl 1:1793-9
references: 19858477
references: Genetics. 2010 Jul;185(3):1097-110
references: 20442220
references: Evolution. 2007 Apr;61(4):902-11
references: 17439620
references: Annu Rev Econom. 2011 Sep;3:291-317
references: 22022635