From 9aa9f76cb16a0e71fea19dd125761034aaca4fd4 Mon Sep 17 00:00:00 2001 From: xiangzhou Date: Mon, 22 Sep 2014 11:12:46 -0400 Subject: version 0.95alpha --- mvlmm.cpp | 3749 ------------------------------------------------------------- 1 file changed, 3749 deletions(-) delete mode 100644 mvlmm.cpp (limited to 'mvlmm.cpp') diff --git a/mvlmm.cpp b/mvlmm.cpp deleted file mode 100644 index 4b910ee..0000000 --- a/mvlmm.cpp +++ /dev/null @@ -1,3749 +0,0 @@ -/* - Genome-wide Efficient Mixed Model Association (GEMMA) - Copyright (C) 2011 Xiang Zhou - - This program is free software: you can redistribute it and/or modify - it under the terms of the GNU General Public License as published by - the Free Software Foundation, either version 3 of the License, or - (at your option) any later version. - - This program is distributed in the hope that it will be useful, - but WITHOUT ANY WARRANTY; without even the implied warranty of - MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the - GNU General Public License for more details. - - You should have received a copy of the GNU General Public License - along with this program. If not, see . - */ - - - -#include -#include -#include - -#include -#include -#include -#include -#include -#include -#include - -#include "gsl/gsl_vector.h" -#include "gsl/gsl_matrix.h" -#include "gsl/gsl_linalg.h" -#include "gsl/gsl_blas.h" - -#include "gsl/gsl_cdf.h" -#include "gsl/gsl_roots.h" -#include "gsl/gsl_min.h" -#include "gsl/gsl_integration.h" - -#include "io.h" -#include "lapack.h" -#include "gzstream.h" - -#ifdef FORCE_FLOAT -#include "lmm_float.h" -#include "mvlmm_float.h" -#else -#include "lmm.h" -#include "mvlmm.h" -#endif - - - -using namespace std; - - -//in this file, X, Y are already transformed (i.e. UtX and UtY) - - -void MVLMM::CopyFromParam (PARAM &cPar) -{ - a_mode=cPar.a_mode; - d_pace=cPar.d_pace; - - file_bfile=cPar.file_bfile; - file_geno=cPar.file_geno; - file_out=cPar.file_out; - path_out=cPar.path_out; - - l_min=cPar.l_min; - l_max=cPar.l_max; - n_region=cPar.n_region; - p_nr=cPar.p_nr; - em_iter=cPar.em_iter; - nr_iter=cPar.nr_iter; - em_prec=cPar.em_prec; - nr_prec=cPar.nr_prec; - crt=cPar.crt; - - Vg_remle_null=cPar.Vg_remle_null; - Ve_remle_null=cPar.Ve_remle_null; - Vg_mle_null=cPar.Vg_mle_null; - Ve_mle_null=cPar.Ve_mle_null; - - time_UtX=0.0; - time_opt=0.0; - - ni_total=cPar.ni_total; - ns_total=cPar.ns_total; - ni_test=cPar.ni_test; - ns_test=cPar.ns_test; - n_cvt=cPar.n_cvt; - - n_ph=cPar.n_ph; - - indicator_idv=cPar.indicator_idv; - indicator_snp=cPar.indicator_snp; - snpInfo=cPar.snpInfo; - - return; -} - - -void MVLMM::CopyToParam (PARAM &cPar) -{ - cPar.time_UtX=time_UtX; - cPar.time_opt=time_opt; - - cPar.Vg_remle_null=Vg_remle_null; - cPar.Ve_remle_null=Ve_remle_null; - cPar.Vg_mle_null=Vg_mle_null; - cPar.Ve_mle_null=Ve_mle_null; - - cPar.VVg_remle_null=VVg_remle_null; - cPar.VVe_remle_null=VVe_remle_null; - cPar.VVg_mle_null=VVg_mle_null; - cPar.VVe_mle_null=VVe_mle_null; - - cPar.beta_remle_null=beta_remle_null; - cPar.se_beta_remle_null=se_beta_remle_null; - cPar.beta_mle_null=beta_mle_null; - cPar.se_beta_mle_null=se_beta_mle_null; - - cPar.logl_remle_H0=logl_remle_H0; - cPar.logl_mle_H0=logl_mle_H0; - return; -} - - -void MVLMM::WriteFiles () -{ - string file_str; - file_str=path_out+"/"+file_out; - file_str+=".assoc.txt"; - - ofstream outfile (file_str.c_str(), ofstream::out); - if (!outfile) {cout<<"error writing file: "<size1; - double d, logdet_Ve=0.0; - - //eigen decomposition of V_e - gsl_matrix *Lambda=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e_temp=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e_h=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e_hi=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *VgVehi=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *U_l=gsl_matrix_alloc (d_size, d_size); - - gsl_matrix_memcpy(V_e_temp, V_e); - EigenDecomp(V_e_temp, U_l, D_l, 0); - - //calculate V_e_h and V_e_hi - gsl_matrix_set_zero(V_e_h); - gsl_matrix_set_zero(V_e_hi); - for (size_t i=0; isize, d_size=D_l->size, dc_size=Qi->size1; - size_t c_size=dc_size/d_size; - - double delta, dl, d1, d2, d, logdet_Q; - - gsl_matrix *Q=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix_set_zero (Q); - - for (size_t i=0; isize, c_size=X->size1, d_size=D_l->size; - - gsl_vector_set_zero (xHiy); - - double x, delta, dl, y, d; - for (size_t i=0; isize, d_size=D_l->size; - double delta, dl, d_u, d_e; - - for (size_t k=0; ksize1, d_size=UltVehiY->size1; - - gsl_matrix *YUX=gsl_matrix_alloc (d_size, c_size); - - gsl_matrix_memcpy (UltVehiBX, UltVehiY); - gsl_matrix_sub (UltVehiBX, UltVehiU); - - gsl_blas_dgemm(CblasNoTrans, CblasTrans, 1.0, UltVehiBX, X, 0.0, YUX); - gsl_blas_dgemm(CblasNoTrans, CblasNoTrans, 1.0, YUX, XXti, 0.0, UltVehiB); - - gsl_matrix_free(YUX); - - return; -} - -void UpdateRL_B (const gsl_vector *xHiy, const gsl_matrix *Qi, gsl_matrix *UltVehiB) -{ - size_t d_size=UltVehiB->size1, c_size=UltVehiB->size2, dc_size=Qi->size1; - - gsl_vector *b=gsl_vector_alloc (dc_size); - - //calculate b=Qiv - gsl_blas_dgemv(CblasNoTrans, 1.0, Qi, xHiy, 0.0, b); - - //copy b to UltVehiB - for (size_t i=0; isize, d_size=U->size1; - - gsl_matrix_set_zero (V_g); - gsl_matrix_set_zero (V_e); - - double delta; - - //calculate the first part: UD^{-1}U^T and EE^T - for (size_t k=0; ksize, c_size=X->size1, d_size=D_l->size, dc_size=Qi->size1; - - gsl_matrix_set_zero(Sigma_uu); - gsl_matrix_set_zero(Sigma_ee); - - double delta, dl, x, d; - - //calculate the first diagonal term - gsl_vector_view Suu_diag=gsl_matrix_diagonal (Sigma_uu); - gsl_vector_view See_diag=gsl_matrix_diagonal (Sigma_ee); - - for (size_t k=0; ksize, d_size=D_l->size, dc_size=Qi->size1; - double logl=0.0, delta, dl, y, d; - - //calculate yHiy+log|H_k| - for (size_t k=0; ksize, c_size=X->size1, d_size=Y->size1; - size_t dc_size=d_size*c_size; - - gsl_matrix *XXt=gsl_matrix_alloc (c_size, c_size); - gsl_matrix *XXti=gsl_matrix_alloc (c_size, c_size); - gsl_vector *D_l=gsl_vector_alloc (d_size); - gsl_matrix *UltVeh=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *UltVehi=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *UltVehiB=gsl_matrix_alloc (d_size, c_size); - gsl_matrix *Qi=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *Sigma_uu=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *Sigma_ee=gsl_matrix_alloc (d_size, d_size); - gsl_vector *xHiy=gsl_vector_alloc (dc_size); - gsl_permutation * pmt=gsl_permutation_alloc (c_size); - - double logl_const=0.0, logl_old=0.0, logl_new=0.0, logdet_Q, logdet_Ve; - int sig; - - //calculate |XXt| and (XXt)^{-1} - gsl_blas_dsyrk (CblasUpper, CblasNoTrans, 1.0, X, 0.0, XXt); - for (size_t i=0; isize, c_size=W->size1, d_size=V_g->size1; - size_t dc_size=d_size*c_size; - double delta, dl, d, d1, d2, dy, dx, dw, logdet_Ve, logdet_Q, p_value; - - gsl_vector *D_l=gsl_vector_alloc (d_size); - gsl_matrix *UltVeh=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *UltVehi=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *Qi=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *WHix=gsl_matrix_alloc (dc_size, d_size); - gsl_matrix *QiWHix=gsl_matrix_alloc(dc_size, d_size); - - gsl_matrix *xPx=gsl_matrix_alloc (d_size, d_size); - gsl_vector *xPy=gsl_vector_alloc (d_size); - //gsl_vector *UltVehiy=gsl_vector_alloc (d_size); - gsl_vector *WHiy=gsl_vector_alloc (dc_size); - - gsl_matrix_set_zero (xPx); - gsl_matrix_set_zero (WHix); - gsl_vector_set_zero (xPy); - gsl_vector_set_zero (WHiy); - - //eigen decomposition and calculate log|Ve| - logdet_Ve=EigenProc (V_g, V_e, D_l, UltVeh, UltVehi); - - //calculate Qi and log|Q| - logdet_Q=CalcQi (eval, D_l, W, Qi); - - //calculate UltVehiY - gsl_blas_dgemm(CblasNoTrans, CblasNoTrans, 1.0, UltVehi, Y, 0.0, UltVehiY); - - //calculate WHix, WHiy, xHiy, xHix - for (size_t i=0; isize, c_size=W->size1, d_size=V_g->size1; - size_t dc_size=d_size*c_size; - double delta, dl, d, dy, dw, logdet_Ve, logdet_Q; - - gsl_vector *D_l=gsl_vector_alloc (d_size); - gsl_matrix *UltVeh=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *UltVehi=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *Qi=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *Qi_temp=gsl_matrix_alloc (dc_size, dc_size); - //gsl_vector *UltVehiy=gsl_vector_alloc (d_size); - gsl_vector *WHiy=gsl_vector_alloc (dc_size); - gsl_vector *QiWHiy=gsl_vector_alloc (dc_size); - gsl_vector *beta=gsl_vector_alloc (dc_size); - gsl_matrix *Vbeta=gsl_matrix_alloc (dc_size, dc_size); - - gsl_vector_set_zero (WHiy); - - //eigen decomposition and calculate log|Ve| - logdet_Ve=EigenProc (V_g, V_e, D_l, UltVeh, UltVehi); - - //calculate Qi and log|Q| - logdet_Q=CalcQi (eval, D_l, W, Qi); - - //calculate UltVehiY - gsl_blas_dgemm(CblasNoTrans, CblasNoTrans, 1.0, UltVehi, Y, 0.0, UltVehiY); - - //calculate WHiy - for (size_t i=0; isize2; j++) { - for (size_t i=0; isize1; i++) { - gsl_matrix_set(B, i, j, gsl_vector_get(beta, j*d_size+i)); - gsl_matrix_set(se_B, i, j, sqrt(gsl_matrix_get(Vbeta, j*d_size+i, j*d_size+i))); - } - } - - //free matrices - gsl_vector_free(D_l); - gsl_matrix_free(UltVeh); - gsl_matrix_free(UltVehi); - gsl_matrix_free(Qi); - gsl_matrix_free(Qi_temp); - gsl_vector_free(WHiy); - gsl_vector_free(QiWHiy); - gsl_vector_free(beta); - gsl_matrix_free(Vbeta); - - return; -} - - - -//below are functions for Newton-Raphson's algorithm - - - - - -//calculate all Hi and return logdet_H=\sum_{k=1}^{n}log|H_k| -//and calculate Qi and return logdet_Q -//and calculate yPy -void CalcHiQi (const gsl_vector *eval, const gsl_matrix *X, const gsl_matrix *V_g, const gsl_matrix *V_e, gsl_matrix *Hi_all, gsl_matrix *Qi, double &logdet_H, double &logdet_Q) -{ - gsl_matrix_set_zero (Hi_all); - gsl_matrix_set_zero (Qi); - logdet_H=0.0; logdet_Q=0.0; - - size_t n_size=eval->size, c_size=X->size1, d_size=V_g->size1; - double logdet_Ve=0.0, delta, dl, d; - - gsl_matrix *mat_dd=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *UltVeh=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *UltVehi=gsl_matrix_alloc (d_size, d_size); - gsl_vector *D_l=gsl_vector_alloc (d_size); - - //calculate D_l, UltVeh and UltVehi - logdet_Ve=EigenProc (V_g, V_e, D_l, UltVeh, UltVehi); - - //calculate each Hi and log|H_k| - logdet_H=(double)n_size*logdet_Ve; - for (size_t k=0; ksize2, d_size=Y->size1; - - for (size_t k=0; ksize2, c_size=X->size1, d_size=Hi_all->size1; - - double d; - - for (size_t k=0; ksize2; - - for (size_t k=0; ksize2, d_size=Y->size1, dc_size=xHi->size1; - - for (size_t k=0; k=d_size || j>=d_size) {cout<<"error in GetIndex."<size; - - double delta, d1, d2; - - for (size_t k=0; ksize, d_size=Hiy->size1; - - double delta, d; - - for (size_t k=0; ksize, dc_size=xHi->size1; - size_t d_size=xHi->size2/n_size; - - double delta; - - gsl_matrix *mat_dcdc=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *mat_dcdc_t=gsl_matrix_alloc (dc_size, dc_size); - - for (size_t k=0; ksize, d_size=Hiy->size1; - - double delta, d_Hiy_i1, d_Hiy_j1, d_Hiy_i2, d_Hiy_j2, d_Hi_i1i2, d_Hi_i1j2, d_Hi_j1i2, d_Hi_j1j2; - - for (size_t k=0; ksize, d_size=Hiy->size1; - - double delta, d_Hiy_i, d_Hiy_j, d_Hi_i1i2, d_Hi_i1j2, d_Hi_j1i2, d_Hi_j1j2; - - for (size_t k=0; ksize, d_size=Hi->size1, dc_size=xHi->size1; - - double delta, d_Hi_i1i2, d_Hi_i1j2, d_Hi_j1i2, d_Hi_j1j2; - - gsl_matrix *mat_dcdc=gsl_matrix_alloc (dc_size, dc_size); - - for (size_t k=0; ksize, d_size=Hi->size1; - double delta, d; - - for (size_t k=0; ksize, d_size=Hi->size1; - double delta, d_Hi_i1i2, d_Hi_i1j2, d_Hi_j1i2, d_Hi_j1j2; - - for (size_t k=0; ksize1, d_size=Hi->size1; - size_t v=GetIndex(i, j, d_size); - - double d; - - //calculate the first part: trace(HiD) - Calc_traceHiD (eval, Hi, i, j, tPD_g, tPD_e); - - //calculate the second part: -trace(HixQixHiD) - for (size_t k=0; ksize1, d_size=Hi->size1; - size_t v_size=d_size*(d_size+1)/2; - size_t v1=GetIndex(i1, j1, d_size), v2=GetIndex(i2, j2, d_size); - - double d; - - //calculate the first part: trace(HiDHiD) - Calc_traceHiDHiD (eval, Hi, i1, j1, i2, j2, tPDPD_gg, tPDPD_ee, tPDPD_ge); - - //calculate the second and third parts: -trace(HixQixHiDHiD)-trace(HiDHixQixHiD) - for (size_t i=0; isize1; - size_t v; - - for (size_t i=0; isize2/eval->size, dc_size=xHi->size1; - size_t v; - - for (size_t i=0; isize1; - size_t v1, v2; - - for (size_t i1=0; i1size2/eval->size, dc_size=xHi->size1; - size_t v1, v2; - - for (size_t i1=0; i1size; - double delta, d_Hi_ij; - - gsl_matrix *mat_dcdc=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *mat_dcdc_temp=gsl_matrix_alloc (dc_size, dc_size); - - for (size_t k=0; ksize1; - size_t v_size=xHiDHix_all_g->size2/dc_size; - - for (size_t i=0; isize2; i++) { - gsl_vector_const_view vec_g=gsl_matrix_const_column (vec_all_g, i); - gsl_vector_const_view vec_e=gsl_matrix_const_column (vec_all_e, i); - - gsl_vector_view Qivec_g=gsl_matrix_column (Qivec_all_g, i); - gsl_vector_view Qivec_e=gsl_matrix_column (Qivec_all_e, i); - - gsl_blas_dgemv (CblasNoTrans, 1.0, Qi, &vec_g.vector, 0.0, &Qivec_g.vector); - gsl_blas_dgemv (CblasNoTrans, 1.0, Qi, &vec_e.vector, 0.0, &Qivec_e.vector); - } - - return; -} - - -//calculate Qi(xHiDHix) for each pair of i j (i<=j) -void Calc_QiMat_all (const gsl_matrix *Qi, const gsl_matrix *mat_all_g, const gsl_matrix *mat_all_e, gsl_matrix *Qimat_all_g, gsl_matrix *Qimat_all_e) -{ - size_t dc_size=Qi->size1; - size_t v_size=mat_all_g->size2/mat_all_g->size1; - - for (size_t i=0; isize1; - size_t v=GetIndex(i, j, d_size); - - double d; - - //first part: ytHiDHiy - Calc_yHiDHiy (eval, Hiy, i, j, yPDPy_g, yPDPy_e); - - //second and third parts: -(yHix)Qi(xHiDHiy)-(yHiDHix)Qi(xHiy) - gsl_vector_const_view xHiDHiy_g=gsl_matrix_const_column (xHiDHiy_all_g, v); - gsl_vector_const_view xHiDHiy_e=gsl_matrix_const_column (xHiDHiy_all_e, v); - - gsl_blas_ddot(QixHiy, &xHiDHiy_g.vector, &d); - yPDPy_g-=d*2.0; - gsl_blas_ddot(QixHiy, &xHiDHiy_e.vector, &d); - yPDPy_e-=d*2.0; - - //fourth part: +(yHix)Qi(xHiDHix)Qi(xHiy) - gsl_vector_const_view xHiDHixQixHiy_g=gsl_matrix_const_column (xHiDHixQixHiy_all_g, v); - gsl_vector_const_view xHiDHixQixHiy_e=gsl_matrix_const_column (xHiDHixQixHiy_all_e, v); - - gsl_blas_ddot(QixHiy, &xHiDHixQixHiy_g.vector, &d); - yPDPy_g+=d; - gsl_blas_ddot(QixHiy, &xHiDHixQixHiy_e.vector, &d); - yPDPy_e+=d; - - return; -} - -//calculate yPDPDPy=y(Hi-HixQixHi)D(Hi-HixQixHi)D(Hi-HixQixHi)y -//yPDPDPy=yHiDHiDHiy -//-(yHix)Qi(xHiDHiDHiy)-(yHiDHiDHix)Qi(xHiy) -//-(yHiDHix)Qi(xHiDHiy) -//+(yHix)Qi(xHiDHix)Qi(xHiDHiy)+(yHiDHix)Qi(xHiDHix)Qi(xHiy) -//+(yHix)Qi(xHiDHiDHix)Qi(xHiy) -//-(yHix)Qi(xHiDHix)Qi(xHiDHix)Qi(xHiy) -void Calc_yPDPDPy (const gsl_vector *eval, const gsl_matrix *Hi, const gsl_matrix *xHi, const gsl_matrix *Hiy, const gsl_vector *QixHiy, const gsl_matrix *xHiDHiy_all_g, const gsl_matrix *xHiDHiy_all_e, const gsl_matrix *QixHiDHiy_all_g, const gsl_matrix *QixHiDHiy_all_e, const gsl_matrix *xHiDHixQixHiy_all_g, const gsl_matrix *xHiDHixQixHiy_all_e, const gsl_matrix *QixHiDHixQixHiy_all_g, const gsl_matrix *QixHiDHixQixHiy_all_e, const gsl_matrix *xHiDHiDHiy_all_gg, const gsl_matrix *xHiDHiDHiy_all_ee, const gsl_matrix *xHiDHiDHiy_all_ge, const gsl_matrix *xHiDHiDHix_all_gg, const gsl_matrix *xHiDHiDHix_all_ee, const gsl_matrix *xHiDHiDHix_all_ge, const size_t i1, const size_t j1, const size_t i2, const size_t j2, double &yPDPDPy_gg, double &yPDPDPy_ee, double &yPDPDPy_ge) -{ - size_t d_size=Hi->size1, dc_size=xHi->size1; - size_t v1=GetIndex(i1, j1, d_size), v2=GetIndex(i2, j2, d_size); - size_t v_size=d_size*(d_size+1)/2; - - double d; - - gsl_vector *xHiDHiDHixQixHiy=gsl_vector_alloc (dc_size); - - //first part: yHiDHiDHiy - Calc_yHiDHiDHiy (eval, Hi, Hiy, i1, j1, i2, j2, yPDPDPy_gg, yPDPDPy_ee, yPDPDPy_ge); - - //second and third parts: -(yHix)Qi(xHiDHiDHiy)-(yHiDHiDHix)Qi(xHiy) - gsl_vector_const_view xHiDHiDHiy_gg1=gsl_matrix_const_column (xHiDHiDHiy_all_gg, v1*v_size+v2); - gsl_vector_const_view xHiDHiDHiy_ee1=gsl_matrix_const_column (xHiDHiDHiy_all_ee, v1*v_size+v2); - gsl_vector_const_view xHiDHiDHiy_ge1=gsl_matrix_const_column (xHiDHiDHiy_all_ge, v1*v_size+v2); - - gsl_vector_const_view xHiDHiDHiy_gg2=gsl_matrix_const_column (xHiDHiDHiy_all_gg, v2*v_size+v1); - gsl_vector_const_view xHiDHiDHiy_ee2=gsl_matrix_const_column (xHiDHiDHiy_all_ee, v2*v_size+v1); - gsl_vector_const_view xHiDHiDHiy_ge2=gsl_matrix_const_column (xHiDHiDHiy_all_ge, v2*v_size+v1); - - gsl_blas_ddot(QixHiy, &xHiDHiDHiy_gg1.vector, &d); - yPDPDPy_gg-=d; - gsl_blas_ddot(QixHiy, &xHiDHiDHiy_ee1.vector, &d); - yPDPDPy_ee-=d; - gsl_blas_ddot(QixHiy, &xHiDHiDHiy_ge1.vector, &d); - yPDPDPy_ge-=d; - - gsl_blas_ddot(QixHiy, &xHiDHiDHiy_gg2.vector, &d); - yPDPDPy_gg-=d; - gsl_blas_ddot(QixHiy, &xHiDHiDHiy_ee2.vector, &d); - yPDPDPy_ee-=d; - gsl_blas_ddot(QixHiy, &xHiDHiDHiy_ge2.vector, &d); - yPDPDPy_ge-=d; - - //fourth part: -(yHiDHix)Qi(xHiDHiy) - gsl_vector_const_view xHiDHiy_g1=gsl_matrix_const_column (xHiDHiy_all_g, v1); - gsl_vector_const_view xHiDHiy_e1=gsl_matrix_const_column (xHiDHiy_all_e, v1); - gsl_vector_const_view QixHiDHiy_g2=gsl_matrix_const_column (QixHiDHiy_all_g, v2); - gsl_vector_const_view QixHiDHiy_e2=gsl_matrix_const_column (QixHiDHiy_all_e, v2); - - gsl_blas_ddot(&xHiDHiy_g1.vector, &QixHiDHiy_g2.vector, &d); - yPDPDPy_gg-=d; - gsl_blas_ddot(&xHiDHiy_e1.vector, &QixHiDHiy_e2.vector, &d); - yPDPDPy_ee-=d; - gsl_blas_ddot(&xHiDHiy_g1.vector, &QixHiDHiy_e2.vector, &d); - yPDPDPy_ge-=d; - - //fifth and sixth parts: +(yHix)Qi(xHiDHix)Qi(xHiDHiy)+(yHiDHix)Qi(xHiDHix)Qi(xHiy) - gsl_vector_const_view QixHiDHiy_g1=gsl_matrix_const_column (QixHiDHiy_all_g, v1); - gsl_vector_const_view QixHiDHiy_e1=gsl_matrix_const_column (QixHiDHiy_all_e, v1); - - gsl_vector_const_view xHiDHixQixHiy_g1=gsl_matrix_const_column (xHiDHixQixHiy_all_g, v1); - gsl_vector_const_view xHiDHixQixHiy_e1=gsl_matrix_const_column (xHiDHixQixHiy_all_e, v1); - gsl_vector_const_view xHiDHixQixHiy_g2=gsl_matrix_const_column (xHiDHixQixHiy_all_g, v2); - gsl_vector_const_view xHiDHixQixHiy_e2=gsl_matrix_const_column (xHiDHixQixHiy_all_e, v2); - - gsl_blas_ddot(&xHiDHixQixHiy_g1.vector, &QixHiDHiy_g2.vector, &d); - yPDPDPy_gg+=d; - gsl_blas_ddot(&xHiDHixQixHiy_g2.vector, &QixHiDHiy_g1.vector, &d); - yPDPDPy_gg+=d; - - gsl_blas_ddot(&xHiDHixQixHiy_e1.vector, &QixHiDHiy_e2.vector, &d); - yPDPDPy_ee+=d; - gsl_blas_ddot(&xHiDHixQixHiy_e2.vector, &QixHiDHiy_e1.vector, &d); - yPDPDPy_ee+=d; - - gsl_blas_ddot(&xHiDHixQixHiy_g1.vector, &QixHiDHiy_e2.vector, &d); - yPDPDPy_ge+=d; - gsl_blas_ddot(&xHiDHixQixHiy_e2.vector, &QixHiDHiy_g1.vector, &d); - yPDPDPy_ge+=d; - - //seventh part: +(yHix)Qi(xHiDHiDHix)Qi(xHiy) - gsl_matrix_const_view xHiDHiDHix_gg=gsl_matrix_const_submatrix (xHiDHiDHix_all_gg, 0, (v1*v_size+v2)*dc_size, dc_size, dc_size); - gsl_matrix_const_view xHiDHiDHix_ee=gsl_matrix_const_submatrix (xHiDHiDHix_all_ee, 0, (v1*v_size+v2)*dc_size, dc_size, dc_size); - gsl_matrix_const_view xHiDHiDHix_ge=gsl_matrix_const_submatrix (xHiDHiDHix_all_ge, 0, (v1*v_size+v2)*dc_size, dc_size, dc_size); - - gsl_blas_dgemv (CblasNoTrans, 1.0, &xHiDHiDHix_gg.matrix, QixHiy, 0.0, xHiDHiDHixQixHiy); - gsl_blas_ddot(xHiDHiDHixQixHiy, QixHiy, &d); - yPDPDPy_gg+=d; - gsl_blas_dgemv (CblasNoTrans, 1.0, &xHiDHiDHix_ee.matrix, QixHiy, 0.0, xHiDHiDHixQixHiy); - gsl_blas_ddot(xHiDHiDHixQixHiy, QixHiy, &d); - yPDPDPy_ee+=d; - gsl_blas_dgemv (CblasNoTrans, 1.0, &xHiDHiDHix_ge.matrix, QixHiy, 0.0, xHiDHiDHixQixHiy); - gsl_blas_ddot(xHiDHiDHixQixHiy, QixHiy, &d); - yPDPDPy_ge+=d; - - //eighth part: -(yHix)Qi(xHiDHix)Qi(xHiDHix)Qi(xHiy) - gsl_vector_const_view QixHiDHixQixHiy_g1=gsl_matrix_const_column (QixHiDHixQixHiy_all_g, v1); - gsl_vector_const_view QixHiDHixQixHiy_e1=gsl_matrix_const_column (QixHiDHixQixHiy_all_e, v1); - - gsl_blas_ddot(&QixHiDHixQixHiy_g1.vector, &xHiDHixQixHiy_g2.vector, &d); - yPDPDPy_gg-=d; - gsl_blas_ddot(&QixHiDHixQixHiy_e1.vector, &xHiDHixQixHiy_e2.vector, &d); - yPDPDPy_ee-=d; - gsl_blas_ddot(&QixHiDHixQixHiy_g1.vector, &xHiDHixQixHiy_e2.vector, &d); - yPDPDPy_ge-=d; - - //free memory - gsl_vector_free(xHiDHiDHixQixHiy); - - return; -} - - -//calculate Edgeworth correctation factors for small samples -//notation and method follows Thomas J. Rothenberg, Econometirca 1984; 52 (4) -//M=xHiDHix -void CalcCRT (const gsl_matrix *Hessian_inv, const gsl_matrix *Qi, const gsl_matrix *QixHiDHix_all_g, const gsl_matrix *QixHiDHix_all_e, const gsl_matrix *xHiDHiDHix_all_gg, const gsl_matrix *xHiDHiDHix_all_ee, const gsl_matrix *xHiDHiDHix_all_ge, const size_t d_size, double &crt_a, double &crt_b, double &crt_c) -{ - crt_a=0.0; crt_b=0.0; crt_c=0.0; - - size_t dc_size=Qi->size1, v_size=Hessian_inv->size1/2; - size_t c_size=dc_size/d_size; - double h_gg, h_ge, h_ee, d, B=0.0, C=0.0, D=0.0; - double trCg1, trCe1, trCg2, trCe2, trB_gg, trB_ge, trB_ee, trCC_gg, trCC_ge, trCC_ee, trD_gg=0.0, trD_ge=0.0, trD_ee=0.0; - - gsl_matrix *QiMQi_g1=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMQi_e1=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMQi_g2=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMQi_e2=gsl_matrix_alloc (dc_size, dc_size); - - gsl_matrix *QiMQisQisi_g1=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *QiMQisQisi_e1=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *QiMQisQisi_g2=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *QiMQisQisi_e2=gsl_matrix_alloc (d_size, d_size); - - gsl_matrix *QiMQiMQi_gg=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMQiMQi_ge=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMQiMQi_ee=gsl_matrix_alloc (dc_size, dc_size); - - gsl_matrix *QiMMQi_gg=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMMQi_ge=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *QiMMQi_ee=gsl_matrix_alloc (dc_size, dc_size); - - gsl_matrix *Qi_si=gsl_matrix_alloc (d_size, d_size); - - gsl_matrix *M_dd=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *M_dcdc=gsl_matrix_alloc (dc_size, dc_size); - - //invert Qi_sub to Qi_si - gsl_matrix *Qi_sub=gsl_matrix_alloc (d_size, d_size); - - gsl_matrix_const_view Qi_s=gsl_matrix_const_submatrix (Qi, (c_size-1)*d_size, (c_size-1)*d_size, d_size, d_size); - - int sig; - gsl_permutation * pmt=gsl_permutation_alloc (d_size); - - gsl_matrix_memcpy (Qi_sub, &Qi_s.matrix); - LUDecomp (Qi_sub, pmt, &sig); - LUInvert (Qi_sub, pmt, Qi_si); - - gsl_permutation_free(pmt); - gsl_matrix_free(Qi_sub); - - //calculate correctation factors - for (size_t v1=0; v1size1, d_size=Hi->size1; - size_t c_size=dc_size/d_size; - size_t v_size=d_size*(d_size+1)/2; - size_t v1, v2; - double dev1_g, dev1_e, dev2_gg, dev2_ee, dev2_ge; - - gsl_matrix *Hessian=gsl_matrix_alloc (v_size*2, v_size*2); - - gsl_matrix *xHiDHiy_all_g=gsl_matrix_alloc (dc_size, v_size); - gsl_matrix *xHiDHiy_all_e=gsl_matrix_alloc (dc_size, v_size); - gsl_matrix *xHiDHix_all_g=gsl_matrix_alloc (dc_size, v_size*dc_size); - gsl_matrix *xHiDHix_all_e=gsl_matrix_alloc (dc_size, v_size*dc_size); - gsl_matrix *xHiDHixQixHiy_all_g=gsl_matrix_alloc (dc_size, v_size); - gsl_matrix *xHiDHixQixHiy_all_e=gsl_matrix_alloc (dc_size, v_size); - - gsl_matrix *QixHiDHiy_all_g=gsl_matrix_alloc (dc_size, v_size); - gsl_matrix *QixHiDHiy_all_e=gsl_matrix_alloc (dc_size, v_size); - gsl_matrix *QixHiDHix_all_g=gsl_matrix_alloc (dc_size, v_size*dc_size); - gsl_matrix *QixHiDHix_all_e=gsl_matrix_alloc (dc_size, v_size*dc_size); - gsl_matrix *QixHiDHixQixHiy_all_g=gsl_matrix_alloc (dc_size, v_size); - gsl_matrix *QixHiDHixQixHiy_all_e=gsl_matrix_alloc (dc_size, v_size); - - gsl_matrix *xHiDHiDHiy_all_gg=gsl_matrix_alloc (dc_size, v_size*v_size); - gsl_matrix *xHiDHiDHiy_all_ee=gsl_matrix_alloc (dc_size, v_size*v_size); - gsl_matrix *xHiDHiDHiy_all_ge=gsl_matrix_alloc (dc_size, v_size*v_size); - gsl_matrix *xHiDHiDHix_all_gg=gsl_matrix_alloc (dc_size, v_size*v_size*dc_size); - gsl_matrix *xHiDHiDHix_all_ee=gsl_matrix_alloc (dc_size, v_size*v_size*dc_size); - gsl_matrix *xHiDHiDHix_all_ge=gsl_matrix_alloc (dc_size, v_size*v_size*dc_size); - - //calculate xHiDHiy_all, xHiDHix_all and xHiDHixQixHiy_all - Calc_xHiDHiy_all (eval, xHi, Hiy, xHiDHiy_all_g, xHiDHiy_all_e); - Calc_xHiDHix_all (eval, xHi, xHiDHix_all_g, xHiDHix_all_e); - Calc_xHiDHixQixHiy_all (xHiDHix_all_g, xHiDHix_all_e, QixHiy, xHiDHixQixHiy_all_g, xHiDHixQixHiy_all_e); - - Calc_xHiDHiDHiy_all (v_size, eval, Hi, xHi, Hiy, xHiDHiDHiy_all_gg, xHiDHiDHiy_all_ee, xHiDHiDHiy_all_ge); - Calc_xHiDHiDHix_all (v_size, eval, Hi, xHi, xHiDHiDHix_all_gg, xHiDHiDHix_all_ee, xHiDHiDHix_all_ge); - - //calculate QixHiDHiy_all, QixHiDHix_all and QixHiDHixQixHiy_all - Calc_QiVec_all (Qi, xHiDHiy_all_g, xHiDHiy_all_e, QixHiDHiy_all_g, QixHiDHiy_all_e); - Calc_QiVec_all (Qi, xHiDHixQixHiy_all_g, xHiDHixQixHiy_all_e, QixHiDHixQixHiy_all_g, QixHiDHixQixHiy_all_e); - Calc_QiMat_all (Qi, xHiDHix_all_g, xHiDHix_all_e, QixHiDHix_all_g, QixHiDHix_all_e); - - double tHiD_g, tHiD_e, tPD_g, tPD_e, tHiDHiD_gg, tHiDHiD_ee, tHiDHiD_ge, tPDPD_gg, tPDPD_ee, tPDPD_ge; - double yPDPy_g, yPDPy_e, yPDPDPy_gg, yPDPDPy_ee, yPDPDPy_ge; - - //calculate gradient and Hessian for Vg - for (size_t i1=0; i11) { - CalcCRT (Hessian_inv, Qi, QixHiDHix_all_g, QixHiDHix_all_e, xHiDHiDHix_all_gg, xHiDHiDHix_all_ee, xHiDHiDHix_all_ge, d_size, crt_a, crt_b, crt_c); - } else { - crt_a=0.0; crt_b=0.0; crt_c=0.0; - } - - gsl_matrix_free(xHiDHiy_all_g); - gsl_matrix_free(xHiDHiy_all_e); - gsl_matrix_free(xHiDHix_all_g); - gsl_matrix_free(xHiDHix_all_e); - gsl_matrix_free(xHiDHixQixHiy_all_g); - gsl_matrix_free(xHiDHixQixHiy_all_e); - - gsl_matrix_free(QixHiDHiy_all_g); - gsl_matrix_free(QixHiDHiy_all_e); - gsl_matrix_free(QixHiDHix_all_g); - gsl_matrix_free(QixHiDHix_all_e); - gsl_matrix_free(QixHiDHixQixHiy_all_g); - gsl_matrix_free(QixHiDHixQixHiy_all_e); - - gsl_matrix_free(xHiDHiDHiy_all_gg); - gsl_matrix_free(xHiDHiDHiy_all_ee); - gsl_matrix_free(xHiDHiDHiy_all_ge); - gsl_matrix_free(xHiDHiDHix_all_gg); - gsl_matrix_free(xHiDHiDHix_all_ee); - gsl_matrix_free(xHiDHiDHix_all_ge); - - return; -} - - -//update Vg, Ve -void UpdateVgVe (const gsl_matrix *Hessian_inv, const gsl_vector *gradient, const double step_scale, gsl_matrix *V_g, gsl_matrix *V_e) -{ - size_t v_size=gradient->size/2, d_size=V_g->size1; - size_t v; - - gsl_vector *vec_v=gsl_vector_alloc (v_size*2); - - double d; - - //vectorize Vg and Ve - for (size_t i=0; isize, c_size=X->size1, d_size=Y->size1; - size_t dc_size=d_size*c_size; - size_t v_size=d_size*(d_size+1)/2; - - double logdet_H, logdet_Q, yPy, logl_const, logl_old=0.0, logl_new=0.0, step_scale; - int sig; - size_t step_iter, flag_pd; - - gsl_matrix *Vg_save=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *Ve_save=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_temp=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *U_temp=gsl_matrix_alloc (d_size, d_size); - gsl_vector *D_temp=gsl_vector_alloc (d_size); - gsl_vector *xHiy=gsl_vector_alloc (dc_size); - gsl_vector *QixHiy=gsl_vector_alloc (dc_size); - gsl_matrix *Qi=gsl_matrix_alloc (dc_size, dc_size); - gsl_matrix *XXt=gsl_matrix_alloc (c_size, c_size); - - gsl_vector *gradient=gsl_vector_alloc (v_size*2); - - //calculate |XXt| and (XXt)^{-1} - gsl_blas_dsyrk (CblasUpper, CblasNoTrans, 1.0, X, 0.0, XXt); - for (size_t i=0; i10 ) && step_iter<10 && t!=0); - - //terminate if change is small - if (t!=0) { - if (logl_newsize1; i++) { - for (size_t j=0; jsize2; j++) { - cout<size, c_size=X->size1, d_size=Y->size1; - double a, b, c; - double lambda, logl, vg, ve; - - //Initial the diagonal elements of Vg and Ve using univariate LMM and REML estimates - gsl_matrix *Xt=gsl_matrix_alloc (n_size, c_size); - gsl_vector *beta_temp=gsl_vector_alloc(c_size); - gsl_vector *se_beta_temp=gsl_vector_alloc(c_size); - - gsl_matrix_transpose_memcpy (Xt, X); - - for (size_t i=0; i4) { - //first obtain good initial values - //large matrices for EM - gsl_matrix *U_hat=gsl_matrix_alloc (2, n_size); - gsl_matrix *E_hat=gsl_matrix_alloc (2, n_size); - gsl_matrix *OmegaU=gsl_matrix_alloc (2, n_size); - gsl_matrix *OmegaE=gsl_matrix_alloc (2, n_size); - gsl_matrix *UltVehiY=gsl_matrix_alloc (2, n_size); - gsl_matrix *UltVehiBX=gsl_matrix_alloc (2, n_size); - gsl_matrix *UltVehiU=gsl_matrix_alloc (2, n_size); - gsl_matrix *UltVehiE=gsl_matrix_alloc (2, n_size); - - //large matrices for NR - gsl_matrix *Hi_all=gsl_matrix_alloc (2, 2*n_size); //each dxd block is H_k^{-1} - gsl_matrix *Hiy_all=gsl_matrix_alloc (2, n_size); //each column is H_k^{-1}y_k - gsl_matrix *xHi_all=gsl_matrix_alloc (2*c_size, 2*n_size); //each dcxdc block is x_k\otimes H_k^{-1} - gsl_matrix *Hessian=gsl_matrix_alloc (6, 6); - - //2 by n matrix of Y - gsl_matrix *Y_sub=gsl_matrix_alloc (2, n_size); - gsl_matrix *Vg_sub=gsl_matrix_alloc (2, 2); - gsl_matrix *Ve_sub=gsl_matrix_alloc (2, 2); - gsl_matrix *B_sub=gsl_matrix_alloc (2, c_size); - - for (size_t i=0; isize1, d_size=UtY->size2, c_size=UtW->size2; - - size_t dc_size=d_size*(c_size+1), v_size=d_size*(d_size+1)/2; - - //large matrices for EM - gsl_matrix *U_hat=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *E_hat=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *OmegaU=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *OmegaE=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiY=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiBX=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiU=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiE=gsl_matrix_alloc (d_size, n_size); - - //large matrices for NR - gsl_matrix *Hi_all=gsl_matrix_alloc (d_size, d_size*n_size); //each dxd block is H_k^{-1} - gsl_matrix *Hiy_all=gsl_matrix_alloc (d_size, n_size); //each column is H_k^{-1}y_k - gsl_matrix *xHi_all=gsl_matrix_alloc (dc_size, d_size*n_size); //each dcxdc block is x_k\otimes H_k^{-1} - gsl_matrix *Hessian=gsl_matrix_alloc (v_size*2, v_size*2); - - gsl_vector *x=gsl_vector_alloc (n_size); - gsl_vector *x_miss=gsl_vector_alloc (n_size); - - gsl_matrix *Y=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *X=gsl_matrix_alloc (c_size+1, n_size); - gsl_matrix *V_g=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *B=gsl_matrix_alloc (d_size, c_size+1); - gsl_vector *beta=gsl_vector_alloc (d_size); - gsl_matrix *Vbeta=gsl_matrix_alloc (d_size, d_size); - - //null estimates for initial values - gsl_matrix *V_g_null=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e_null=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *B_null=gsl_matrix_alloc (d_size, c_size+1); - gsl_matrix *se_B_null=gsl_matrix_alloc (d_size, c_size); - - gsl_matrix_view X_sub=gsl_matrix_submatrix (X, 0, 0, c_size, n_size); - gsl_matrix_view B_sub=gsl_matrix_submatrix (B, 0, 0, d_size, c_size); - gsl_matrix_view xHi_all_sub=gsl_matrix_submatrix (xHi_all, 0, 0, d_size*c_size, d_size*n_size); - - gsl_matrix_transpose_memcpy (Y, UtY); - - gsl_matrix_transpose_memcpy (&X_sub.matrix, UtW); - - gsl_vector_view X_row=gsl_matrix_row(X, c_size); - gsl_vector_set_zero(&X_row.vector); - gsl_vector_view B_col=gsl_matrix_column(B, c_size); - gsl_vector_set_zero(&B_col.vector); - - MphInitial(em_iter, em_prec, nr_iter, nr_prec, eval, &X_sub.matrix, Y, l_min, l_max, n_region, V_g, V_e, &B_sub.matrix); - logl_H0=MphEM ('R', em_iter, em_prec, eval, &X_sub.matrix, Y, U_hat, E_hat, OmegaU, OmegaE, UltVehiY, UltVehiBX, UltVehiU, UltVehiE, V_g, V_e, &B_sub.matrix); - logl_H0=MphNR ('R', nr_iter, nr_prec, eval, &X_sub.matrix, Y, Hi_all, &xHi_all_sub.matrix, Hiy_all, V_g, V_e, Hessian, crt_a, crt_b, crt_c); - MphCalcBeta (eval, &X_sub.matrix, Y, V_g, V_e, UltVehiY, &B_sub.matrix, se_B_null); - - c=0; - Vg_remle_null.clear(); - Ve_remle_null.clear(); - for (size_t i=0; isize1; i++) { - for (size_t j=0; jsize2; j++) { - beta_remle_null.push_back(gsl_matrix_get(B, i, j) ); - se_beta_remle_null.push_back(gsl_matrix_get(se_B_null, i, j) ); - } - } - logl_remle_H0=logl_H0; - - cout.setf(std::ios_base::fixed, std::ios_base::floatfield); - cout.precision(4); - - cout<<"REMLE estimate for Vg in the null model: "<1) { - gsl_vector_set(x, i, 2-geno); - } - } - - //calculate statistics - time_start=clock(); - gsl_blas_dgemv (CblasTrans, 1.0, U, x, 0.0, &X_row.vector); - time_UtX+=(clock()-time_start)/(double(CLOCKS_PER_SEC)*60.0); - - //initial values - gsl_matrix_memcpy (V_g, V_g_null); - gsl_matrix_memcpy (V_e, V_e_null); - gsl_matrix_memcpy (B, B_null); - - time_start=clock(); - - //3 is before 1 - if (a_mode==3 || a_mode==4) { - p_score=MphCalcP (eval, &X_row.vector, &X_sub.matrix, Y, V_g_null, V_e_null, UltVehiY, beta, Vbeta); - if (p_score1) {gsl_vector_scale(beta, -1.0);} - - time_opt+=(clock()-time_start)/(double(CLOCKS_PER_SEC)*60.0); - - //store summary data - //SUMSTAT SNPs={snpInfo[t].get_chr(), snpInfo[t].get_rs(), snpInfo[t].get_pos(), n_miss, beta, se, lambda_remle, lambda_mle, p_wald, p_lrt, p_score}; - for (size_t i=0; i b; - - // double lambda_mle=0, lambda_remle=0, beta=0, se=0, ; - double logl_H0=0.0, logl_H1=0.0, p_wald=0, p_lrt=0, p_score=0; - double crt_a, crt_b, crt_c; - int n_bit, n_miss, ci_total, ci_test; - double geno, x_mean; - size_t c=0; - // double s=0.0; - size_t n_size=UtY->size1, d_size=UtY->size2, c_size=UtW->size2; - size_t dc_size=d_size*(c_size+1), v_size=d_size*(d_size+1)/2; - - //large matrices for EM - gsl_matrix *U_hat=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *E_hat=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *OmegaU=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *OmegaE=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiY=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiBX=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiU=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *UltVehiE=gsl_matrix_alloc (d_size, n_size); - - //large matrices for NR - gsl_matrix *Hi_all=gsl_matrix_alloc (d_size, d_size*n_size); //each dxd block is H_k^{-1} - gsl_matrix *Hiy_all=gsl_matrix_alloc (d_size, n_size); //each column is H_k^{-1}y_k - gsl_matrix *xHi_all=gsl_matrix_alloc (dc_size, d_size*n_size); //each dcxdc block is x_k\otimes H_k^{-1} - gsl_matrix *Hessian=gsl_matrix_alloc (v_size*2, v_size*2); - - gsl_vector *x=gsl_vector_alloc (n_size); - - gsl_matrix *Y=gsl_matrix_alloc (d_size, n_size); - gsl_matrix *X=gsl_matrix_alloc (c_size+1, n_size); - gsl_matrix *V_g=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *B=gsl_matrix_alloc (d_size, c_size+1); - gsl_vector *beta=gsl_vector_alloc (d_size); - gsl_matrix *Vbeta=gsl_matrix_alloc (d_size, d_size); - - //null estimates for initial values - gsl_matrix *V_g_null=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *V_e_null=gsl_matrix_alloc (d_size, d_size); - gsl_matrix *B_null=gsl_matrix_alloc (d_size, c_size+1); - gsl_matrix *se_B_null=gsl_matrix_alloc (d_size, c_size); - - gsl_matrix_view X_sub=gsl_matrix_submatrix (X, 0, 0, c_size, n_size); - gsl_matrix_view B_sub=gsl_matrix_submatrix (B, 0, 0, d_size, c_size); - gsl_matrix_view xHi_all_sub=gsl_matrix_submatrix (xHi_all, 0, 0, d_size*c_size, d_size*n_size); - - gsl_matrix_transpose_memcpy (Y, UtY); - gsl_matrix_transpose_memcpy (&X_sub.matrix, UtW); - - gsl_vector_view X_row=gsl_matrix_row(X, c_size); - gsl_vector_set_zero(&X_row.vector); - gsl_vector_view B_col=gsl_matrix_column(B, c_size); - gsl_vector_set_zero(&B_col.vector); - - //time_start=clock(); - MphInitial(em_iter, em_prec, nr_iter, nr_prec, eval, &X_sub.matrix, Y, l_min, l_max, n_region, V_g, V_e, &B_sub.matrix); - - logl_H0=MphEM ('R', em_iter, em_prec, eval, &X_sub.matrix, Y, U_hat, E_hat, OmegaU, OmegaE, UltVehiY, UltVehiBX, UltVehiU, UltVehiE, V_g, V_e, &B_sub.matrix); - logl_H0=MphNR ('R', nr_iter, nr_prec, eval, &X_sub.matrix, Y, Hi_all, &xHi_all_sub.matrix, Hiy_all, V_g, V_e, Hessian, crt_a, crt_b, crt_c); - MphCalcBeta (eval, &X_sub.matrix, Y, V_g, V_e, UltVehiY, &B_sub.matrix, se_B_null); - //cout<<"time for REML in the null = "<<(clock()-time_start)/(double(CLOCKS_PER_SEC)*60.0)<size1; i++) { - for (size_t j=0; jsize2; j++) { - beta_remle_null.push_back(gsl_matrix_get(B, i, j) ); - se_beta_remle_null.push_back(gsl_matrix_get(se_B_null, i, j) ); - } - } - logl_remle_H0=logl_H0; - - cout.setf(std::ios_base::fixed, std::ios_base::floatfield); - cout.precision(4); - cout<<"REMLE estimate for Vg in the null model: "<=0) {break;} - //if (snpInfo[t].rs_number!="MAG18140902") {continue;} - //cout<1) { - gsl_vector_set(x, i, 2-geno); - } - } - - /* - if (t==0) { - ofstream outfile ("./snp1.txt", ofstream::out); - if (!outfile) {cout<<"error writing file: "<size; i++) { - outfile<1) {gsl_vector_scale(beta, -1.0);} - - time_opt+=(clock()-time_start)/(double(CLOCKS_PER_SEC)*60.0); - - //store summary data - //SUMSTAT SNPs={snpInfo[t].get_chr(), snpInfo[t].get_rs(), snpInfo[t].get_pos(), n_miss, beta, se, lambda_remle, lambda_mle, p_wald, p_lrt, p_score}; - for (size_t i=0; i