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//////////////////////////////////////////////////////////////////
// //
// PLINK (c) 2005-2009 Shaun Purcell //
// //
// This file is distributed under the GNU General Public //
// License, Version 2. Please see the file COPYING for more //
// details //
// //
//////////////////////////////////////////////////////////////////
#include <iostream>
#include <iomanip>
#include <cmath>
#include <sstream>
#include "whap.h"
#include "helper.h"
#include "plink.h"
#include "options.h"
#include "perm.h"
#include "nlist.h"
#include "phase.h"
#include "model.h"
#include "linear.h"
#include "logistic.h"
#include "stats.h"
//////////////////////////////////////////////////////////////
// Implements --hap-logistic and --hap-linear functions
// Use framework provided by --chap/whap.cpp
// can perform either omnibus or haplotype specific tests
vector_t Plink::glmHaplotypeTest(bool print, Perm & perm)
{
///////////////////////////////////////////////
// //
// Some basic setup first //
// //
///////////////////////////////////////////////
// Use basic GLM function to fit linear and logistic
// models: although, let it know that there will not
// be a 'main' SNP
par::assoc_glm_without_main_snp = true;
// Return a single result
vector_t results;
// Haplotypes at this position have already been phased
// Record the number of common haplotypes
int nch = 0;
set<int> commonHaplotypes;
for (int h=0; h < haplo->nh; h++)
if ( haplo->f[h] >= par::min_hf )
{
++nch;
commonHaplotypes.insert(h);
}
// if ( ! par::test_hap_GLM_omnibus )
// haplo->HTEST << setw( haplo->ns + 1 ) << haplo->haplotypeName(0) << " ";
if ( nch < 2 )
{
haplo->HTEST << setw(4) << haplo->ns << " "
<< setw(4) << nch << " "
<< setw(4) << locus[haplo->S[0]]->chr << " "
<< setw(12) << locus[haplo->S[0]]->bp << " "
<< setw(12) << locus[haplo->S[haplo->ns-1]]->bp << " "
<< setw(par::pp_maxsnp) << locus[haplo->S[0]]->name << " "
<< setw(par::pp_maxsnp) << locus[haplo->S[haplo->ns-1]]->name << " ";
if ( ! par::test_hap_GLM_omnibus )
{
if ( nch==1 )
haplo->HTEST << setw(12) << haplo->haplotypeName(0) << " ";
else
haplo->HTEST << setw(12) << "NA" << " ";
haplo->HTEST << setw(8) << "NA" << " "
<< setw(8) << "NA" << " "
<< setw(8) << "NA" << " "
<< setw(8) << "NA" << "\n";
}
else
haplo->HTEST << setw(8) << "NA" << " "
<< setw(8) << "NA" << "\n";
results.push_back( 0 );
return results;
}
// Single SNP association
if ( par::test_hap_GLM_omnibus )
{
haplo->HTEST << setw(4) << haplo->ns << " "
<< setw(4) << nch << " "
<< setw(4) << locus[haplo->S[0]]->chr << " "
<< setw(12) << locus[haplo->S[0]]->bp << " "
<< setw(12) << locus[haplo->S[haplo->ns-1]]->bp << " "
<< setw(par::pp_maxsnp) << locus[haplo->S[0]]->name << " "
<< setw(par::pp_maxsnp) << locus[haplo->S[haplo->ns-1]]->name << " ";
// H-1 omnibus (H0 is ref.)
haplo->sets.clear();
set<int>::iterator i = commonHaplotypes.begin();
// Skip first haplotype (this is reference)
// All rare haplotypes will therefore be
// lumped in with the reference
++i;
while ( i != commonHaplotypes.end() )
{
haplo->sets.insert(*i);
++i;
}
// Fit model
glmAssoc(false,*pperm);
// Report results
haplo->result = model->isValid() ? model->getStatistic() : 0;
haplo->pvalue = par::bt ?
chiprobP(haplo->result,1) : ((LinearModel*)model)->getPValue();
// Calculate omnibus tests of H-1 terms
// Assumes the terms are: e.g. for 4 haplotypes
// 0 intercept
// 1 haplotype 2 of H
// 2 haplotype 3 of H
// 3 haplotype 4 of H
int df = nch-1;
vector_t h;
h.resize(df,0);
matrix_t H;
sizeMatrix(H,df,model->getNP());
for (int j=0; j<df; j++)
H[j][j+1] = 1;
double chisq = model->isValid() ? model->linearHypothesis(H,h) : 0;
double pvalue = chiprobP(chisq,df);
if ( model->isValid() )
{
haplo->HTEST << setw(8) << chisq << " "
<< setw(8) << pvalue << "\n";
}
else
{
haplo->HTEST << setw(8) << "NA" << " "
<< setw(8) << "NA" << "\n";
}
// Clean up
delete model;
// Return 1-p, as will be different DF for different windows
results.push_back( 1 - pvalue );
return results;
}
// Otherwise, we are performing H haplotype specific tests
set<int>::iterator i = commonHaplotypes.begin();
while ( i != commonHaplotypes.end() )
{
haplo->sets.clear();
haplo->sets.insert(*i);
// Fit model
glmAssoc(false,*pperm);
// Report results
vector_t coef = model->getCoefs();
// Note: the different direction of OR
haplo->odds = par::bt ? exp(coef[1]) : coef[1];
haplo->result = model->isValid() ? model->getStatistic() : 0;
haplo->pvalue = par::bt ? chiprobP(haplo->result,1) : ((LinearModel*)model)->getPValue();
// Calculate omnibus tests of H-1 terms
haplo->HTEST << setw(4) << haplo->ns << " "
<< setw(4) << nch << " "
<< setw(4) << locus[haplo->S[0]]->chr << " "
<< setw(12) << locus[haplo->S[0]]->bp << " "
<< setw(12) << locus[haplo->S[haplo->ns-1]]->bp << " "
<< setw(par::pp_maxsnp) << locus[haplo->S[0]]->name << " "
<< setw(par::pp_maxsnp) << locus[haplo->S[haplo->ns-1]]->name << " ";
haplo->HTEST << setw(12) << haplo->haplotypeName(*i) << " "
<< setw(8) << haplo->f[*i] << " ";
if ( model->isValid() )
{
haplo->HTEST << setw(8) << haplo->odds << " "
<< setw(8) << haplo->result << " "
<< setw(8) << haplo->pvalue << "\n";
}
else
{
haplo->HTEST << setw(8) << "NA" << " "
<< setw(8) << "NA" << " "
<< setw(8) << "NA" << "\n";
}
// Clean up
delete model;
// Return chi-sq (always 1df)
results.push_back( haplo->result );
// Next common haplotype
++i;
}
return results;
}
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