Cholesky decomposition May 27th 2015 Helsinki, Finland E. Vuoksimaa.

Slides:



Advertisements
Similar presentations
Multivariate Twin Analysis
Advertisements

Bivariate analysis HGEN619 class 2007.
Fitting Bivariate Models October 21, 2014 Elizabeth Prom-Wormley & Hermine Maes
The use of Cholesky decomposition in multivariate models of sex-limited genetic and environmental effects Michael C. Neale Virginia Institute for Psychiatric.
Univariate Model Fitting
Multivariate Mx Exercise D Posthuma Files: \\danielle\Multivariate.
Estimating “Heritability” using Genetic Data David Evans University of Queensland.
Factor analysis Caroline van Baal March 3 rd 2004, Boulder.
(Re)introduction to OpenMx Sarah Medland. Starting at the beginning  Opening R Gui – double click Unix/Terminal – type R  Closing R Gui – click on the.
Path Analysis Danielle Dick Boulder Path Analysis Allows us to represent linear models for the relationships between variables in diagrammatic form.
Multivariate Analysis Nick Martin, Hermine Maes TC21 March 2008 HGEN619 10/20/03.
Introduction to Multivariate Analysis Frühling Rijsdijk & Shaun Purcell Twin Workshop 2004.
Multivariate Genetic Analysis: Introduction(II) Frühling Rijsdijk & Shaun Purcell Wednesday March 6, 2002.
Developmental models. Multivariate analysis choleski models factor models –y =  f + u genetic factor models –P j = h G j + c C j + e E j –common pathway.
Multiple raters March 7 th, 2002 Boulder, Colorado John Hewitt.
Longitudinal Modeling Nathan, Lindon & Mike LongitudinalTwinAnalysis_MatrixRawCon.R GenEpiHelperFunctions.R jepq.txt.
Univariate Analysis in Mx Boulder, Group Structure Title Type: Data/ Calculation/ Constraint Reading Data Matrices Declaration Assigning Specifications/
Multivariate Analysis Hermine Maes TC19 March 2006 HGEN619 10/20/03.
David M. Evans Sarah E. Medland Developmental Models in Genetic Research Wellcome Trust Centre for Human Genetics Oxford United Kingdom Twin Workshop Boulder.
Univariate Analysis Hermine Maes TC19 March 2006.
Gene x Environment Interactions Brad Verhulst (With lots of help from slides written by Hermine and Liz) September 30, 2014.
Introduction to Multivariate Genetic Analysis Kate Morley and Frühling Rijsdijk 21st Twin and Family Methodology Workshop, March 2008.
Path Analysis Frühling Rijsdijk. Biometrical Genetic Theory Aims of session:  Derivation of Predicted Var/Cov matrices Using: (1)Path Tracing Rules (2)Covariance.
Karri Silventoinen University of Helsinki Osaka University.
Standard genetic simplex models in the classical twin design with phenotype to E transmission Conor Dolan & Janneke de Kort Biological Psychology, VU 1.
Karri Silventoinen University of Helsinki Osaka University.
Continuously moderated effects of A,C, and E in the twin design Conor V Dolan & Sanja Franić (BioPsy VU) Boulder Twin Workshop March 4, 2014 Based on PPTs.
 Go to Faculty/marleen/Boulder2012/Moderating_cov  Copy all files to your own directory  Go to Faculty/sanja/Boulder2012/Moderating_covariances _IQ_SES.
Introduction to Multivariate Genetic Analysis (2) Marleen de Moor, Kees-Jan Kan & Nick Martin March 7, 20121M. de Moor, Twin Workshop Boulder.
Extending Simplex model to model Ph  E transmission JANNEKE m. de kort & C.V. DolAn Contact:
Univariate modeling Sarah Medland. Starting at the beginning… Data preparation – The algebra style used in Mx expects 1 line per case/family – (Almost)
Practical SCRIPT: F:\meike\2010\Multi_prac\MultivariateTwinAnalysis_MatrixRaw.r DATA: DHBQ_bs.dat.
Longitudinal Modeling Nathan Gillespie & Dorret Boomsma \\nathan\2008\Longitudinal neuro_f_chol.mx neuro_f_simplex.mx jepq6.dat.
The importance of the “Means Model” in Mx for modeling regression and association Dorret Boomsma, Nick Martin Boulder 2008.
Gene-Environment Interaction & Correlation Danielle Dick & Danielle Posthuma Leuven 2008.
Threshold Liability Models (Ordinal Data Analysis) Frühling Rijsdijk MRC SGDP Centre, Institute of Psychiatry, King’s College London Boulder Twin Workshop.
Univariate Analysis Hermine Maes TC21 March 2008.
Longitudinal Modeling Nathan & Lindon Template_Developmental_Twin_Continuous_Matrix.R Template_Developmental_Twin_Ordinal_Matrix.R jepq.txt GenEpiHelperFunctions.R.
Mx modeling of methylation data: twin correlations [means, SD, correlation] ACE / ADE latent factor model regression [sex and age] genetic association.
Mx Practical TC20, 2007 Hermine H. Maes Nick Martin, Dorret Boomsma.
David M. Evans Multivariate QTL Linkage Analysis Queensland Institute of Medical Research Brisbane Australia Twin Workshop Boulder 2003.
Continuous heterogeneity Danielle Dick & Sarah Medland Boulder Twin Workshop March 2006.
Frühling Rijsdijk & Kate Morley
Introduction to Multivariate Genetic Analysis Danielle Posthuma & Meike Bartels.
Developmental Models/ Longitudinal Data Analysis Danielle Dick & Nathan Gillespie Boulder, March 2006.
QTL Mapping Using Mx Michael C Neale Virginia Institute for Psychiatric and Behavioral Genetics Virginia Commonwealth University.
March 7, 2012M. de Moor, Twin Workshop Boulder1 Copy files Go to Faculty\marleen\Boulder2012\Multivariate Copy all files to your own directory Go to Faculty\kees\Boulder2012\Multivariate.
Multivariate Genetic Analysis (Introduction) Frühling Rijsdijk Wednesday March 8, 2006.
Invest. Ophthalmol. Vis. Sci ;57(1): doi: /iovs Figure Legend:
Genetic simplex model: practical
Multivariate Analysis
Bivariate analysis HGEN619 class 2006.
Introduction to Multivariate Genetic Analysis
Re-introduction to openMx
Heterogeneity HGEN619 class 2007.
Longitudinal Analysis
Path Analysis Danielle Dick Boulder 2008
Behavior Genetics The Study of Variation and Heredity
Univariate modeling Sarah Medland.
(Re)introduction to Mx Sarah Medland
Longitudinal Modeling
Sarah Medland faculty/sarah/2018/Tuesday
Getting more from multivariate data: Multiple raters (or ratings)
Bivariate Genetic Analysis Practical
Multivariate Genetic Analysis
Multivariate Genetic Analysis: Introduction
Rater Bias & Sibling Interaction Meike Bartels Boulder 2004
Presentation transcript:

Cholesky decomposition May 27th 2015 Helsinki, Finland E. Vuoksimaa

Univariate & multivariate approach Univariate models – A,C and E estimates Bivariate Cholesky – A,C and E estimates & covariance between two phenotypes – ACE more power compared to univariate scenario – two interpretations on the relationship between two phenotypes 1) how much of the variance is explained by A,C,E effect that are shared between phenotypes 2) decomposing phenotypic correlation into genetic and environmental correlations

Multivariate models – A, C and E estimates & covariance between phenotypes: trivariate & other multivariate Cholesky decompositions  extension of bivariate Cholesky; Independent (IP) (biometric) & common pathway (CP) models – testing against ACE Cholesky – Cholesky for genetic or environmental effects: e.g., Cholesky structure for C and CP for A and E

Example data Height (measured), weight (measured) also general cognitive ability (GCA, in-person neuropsychological testing, IQ based on two WAIS subtests) Residualized measures (age and sex) Standardized M=0, SD=1

Bivariate Vars <- c(’var1',’var2') nv <- 2 # number of variables ntv <- nv*2 # number of total variables selVars <- paste(Vars,c(rep(1,nv),rep(2,nv)),sep="") pathA <- mxMatrix( type="Lower", nrow=nv, ncol=nv, free=TRUE, values= ?, lbound=?, ubound=? name="a" ) pathC <- mxMatrix( type="Lower", nrow=nv, ncol=nv, free=TRUE, values= ?, lbound=?, ubound=? name=”c" ) pathE <- mxMatrix( type="Lower", nrow=nv, ncol=nv, free=TRUE, values= ?, lbound=?, ubound=? name=”c" )

Bivariate Cholesky AA HeightGCA AA Height GCA rg Correlated factors rg = genetic correlation

Bivariate Cholesky CC HeightGCA CC Height GCA rc Correlated factors rc = common enviromental correlation

Bivariate Cholesky EE HeightGCA EE Height GCA re Correlated factors re = unique environmental correlation

Cholesky decomposition A A HeightGCA A A Height GCA C C C C E E E E 1.0 MZ / 0.5 DZ 1.0 MZ / 1.0 DZ

Correlated factors A A HeightGCA A A Height GCA C C C C E E E E rc rg re

Additive genetic effects AA Height GCA a11 a21 a22 A1A2 Heighta11 GCAa21a22 omxSetParameters( CholAeModel_noAcor, labels=labLower("a",nv), free=c(TRUE,FALSE,TRUE)) Lower nvar x nvar matrix  parameters are estimated freely shared genetic effects can be constrained to zero (0): [nvar X (nvar+1)] / 2 = number of A paths  (2 X 3) / 2 = 3

Additive genetic effects CC Height GCA c11 c21 c22 C1C2 Heightc11 GCAc21c22 omxSetParameters( CholAeModel_noCcor, labels=labLower(”c",nv), free=c(TRUE,FALSE,TRUE)) Lower nvar x nvar matrix  parameters are estimated freely shared common environmental effects can be constrained to zero (0): [nvar X (nvar+1)] / 2 = number of C paths  (2 X 3) / 2 = 3

Additive genetic effects EE Height GCA e11 e21 e22 E1E2 Heighte11 GCAe21e22 omxSetParameters( CholAeModel_noEcor, labels=labLower(”e",nv), free=c(TRUE,FALSE,TRUE)) Lower nvar x nvar matrix  parameters are estimated freely shared unique environmental effects can be constrained to zero (0): [nvar X (nvar+1)] / 2 = number of E paths  (2 X 3) / 2 = 3

Number of parameters [nvar X (nvar+1)] / 2 = number of A paths  (2 X 3) / 2 = 3 [nvar X (nvar+1)] / 2 = number of C paths  (2 X 3) / 2 = 3 [nvar X (nvar+1)] / 2 = number of E paths  (2 X 3) / 2 = 3 means = 2 Bivariate number of parameters = 11 Number of parameters in AE-AE cholesky ? Number of parameters in AE-AE cholesky where rg = 0 ?

Proportion of phenotypic correlation due to rg (√a 2 var1 X rg X √a 2 var2) / rp  (√ heritability of phenotype 1 X genetic correlation between phenotype 1 and phenotype 2 X √ heritability of phenotype 2) / phenotypic correlation

Trivariate Vars <- c(’var1',’var2’, ’var3’)# add 3rd variable, 4th, 5th, etc. nv <- 3 # number of variables# you need to change this, here 3 ntv <- nv*2 # number of total variables selVars <- paste(Vars,c(rep(1,nv),rep(2,nv)),sep="") pathA <- mxMatrix( type="Lower", nrow=nv, ncol=nv, free=TRUE, values= ?, lbound=?, ubound=? name="a" ) pathC <- mxMatrix( type="Lower", nrow=nv, ncol=nv, free=TRUE, values= ?, lbound=?, ubound=? name=”c" ) pathE <- mxMatrix( type="Lower", nrow=nv, ncol=nv, free=TRUE, values= ?, lbound=?, ubound=? name=”c" ) Matrices to get the path coefficients for a, c and e

Trivariate Cholesky decompostion A A Var1 Var2 a11 a21 a22 A1A2A3 Var1a11 Var2a21a22 Var3a31a32a33 Lower nvar x nvar matrix  parameters are estimated freely Var3 a31 A a32 a33 [nvar X (nvar+1)] / 2 = number of A paths  (3 X 4) / 2 = 6

Trivariate Cholesky decompostion C C Var1 Var2 c11 c21 c22 A1A2A3 Var1c11 Var2c21c22 Var3c31c32c33 Lower nvar x nvar matrix  parameters are estimated freely Var3 c31 C c32 c33 [nvar X (nvar+1)] / 2 = number of C paths  (3 X 4) / 2 = 6

Trivariate Cholesky decompostion E E Var1 Var2 e11 e21 e22 A1A2A3 Var1e11 Var2e21e22 Var3e31e32e33 Lower nvar x nvar matrix  parameters are estimated freely Var3 e31 E e32 e33 [nvar X (nvar+1)] / 2 = number of E paths  (3 X 4) / 2 = 6

Trivariate correlated factors A A Var1 Var2Var3 A

Trivariate correlated factors C C Var1 Var2Var3 C

Trivariate correlated factors E E Var1 Var2Var3 E

Number of parameters [nvar X (nvar+1)] / 2 = number of A paths [nvar X (nvar+1)] / 2 = number of C paths [nvar X (nvar+1)] / 2 = number of E paths means Trivariate number of parameters = ?

Included in the example script Saturated models are included in the script ACE-ACE Cholesky AE-AE Cholesky CE-CE Cholesky rg = 0 re = 0 no correlation between phenotypes

Bivariate with height & weight, also height & GCA and weight & GCA Calculate genetic and environmental correlations Can we set rg/re or both as zero? What is the proportion of phenotypic correlation due to rg?

Things to consider Do not automatically run AE-AE after ACE-ACE, e.g., consider if you want to keep C effects for one(/some) of the variables E.g., C effects of about 15% may be fixed to be zero, but you may still want to keep the C effects – less biased genetic correlation Cholesky in context of IP and CP models What is the question that you are asking

Suggested reading Carey G. (1988), Behavior Genetics, 18, Loehlin (1996). The Cholesky approach: a cautionary note. Behavior Genetics, 26, Carey G. (2005). Cholesky problems. Behavior Genetics, 35, Wu and Neale (2013). On the likelihood ratio tests in bivariate ACDE models. Psychometrika, 78, Panizzon et al. (2014). Genetic and environmental influences on general cognitive ability: is g a valid latent construct. Intelligence, 43,

Resources including presentations International Twin workshop, every March, Institute for behavioral genetics, University of Boulder Colorado QIMR, Workshop, Sarah Medland