!QTL analysis via weighted likelihood of three covariance matrices !Using marker6 !Using MZ and DZ twins !Analysis of platelet count !Twelve, fourteen and sixteen year olds #define nvar 3 ! multivariate #define nsib 2 ! number of siblings #NGroups 3 G1: Parameter Estimates Calculation Begin Matrices; X Lower nvar nvar Free !genetic background W Lower nvar nvar Free !dominance Z Lower nvar nvar Free !unique environment L Full nvar 1 Free !QTL effect M Full nsib nvar Free !means H Full 1 1 R Full 1 1 End Matrices; Specify M 40 41 42 40 41 42 Matrix H .5 Matrix R .25 Begin Algebra; A= X*X'; !additive genetic variance D= W*W'; !dominance variance E= Z*Z'; !unique environmental variance Q= L*L'; !variance due to QTL V= A+Q+D+E; !total variance End Algebra; End G2: Monozygotic twins Data NInput=13 Rectangular File=marker6.dat Labels famid indid1 indid2 pibd0 pibd1 pibd2 zygosity plt11 plt12 plt13 plt21 plt22 plt23 Select if zygosity <3; Select plt11 plt12 plt13 plt21 plt22 plt23; Begin Matrices = Group 1; Means M; Covariance A+D+Q+E | A+D+Q _ A+D+Q | A+D+Q+E; End; G3: Dizygotic twins Data NInput=13 NModel=3 Rectangular File=marker6.dat Labels famid indid1 indid2 pibd0 pibd1 pibd2 zygosity plt11 plt12 plt13 plt21 plt22 plt23 Select if zygosity >2; Select pibd0 pibd1 pibd2 plt11 plt12 plt13 plt21 plt22 plt23; Definition pibd0 pibd1 pibd2; Begin Matrices = Group 1; K Full 3 1 !IBD probabilities (from Genehunter) I Unit 3 1 !to create means for all models & sibs End Matrices; Specify K pibd0 pibd1 pibd2 Begin Algebra; U= H@A+R@D; !IBD 0 covariance (=non-qtl covariance) O= U+H@Q; !IBD 1 covariance P= U+Q; !IBD 2 covariance Y= V|U_ U|V_ !IBD 0 matrix V|O_ O|V_ !IBD 1 matrix V|P_ P|V; !IBD 2 matrix End Algebra; Means I@M; Covariance Y; Weights K; Start 1 All Start 2.8 M 1 1 1 to M 1 nsib nvar Option NDecimals=3 Option Iterations=5000 Option Multiple Issat End ! Equate loadings on QTL Equate L 1 1 1 L 1 2 1 L 1 3 1 End ! Test significance of QTL effect Drop L 1 1 1 to L 1 3 1 End