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SMR_data_p4.cpp
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/*
* SMR_data_p4.cpp
* Implementations of univariable and multivariable MR-IVW implementations
*
* 2020 by Marie Sadler
*
* This file is distributed under the GNU General Public
* License, Version 2.
*/
#include "SMR_data_p4.h"
namespace SMRDATA
{
void lookup_dense(char* outFileName,char* eqtlFileName, char* snplstName, char* problstName,char* genelistName, double plookup, int chr, int prbchr,int snpchr, char* snprs, char* fromsnprs, char* tosnprs, char* prbname, char* fromprbname, char* toprbname,int snpWind, int prbWind,char* genename,int fromsnpkb, int tosnpkb, int fromprbkb, int toprbkb, bool snpwindFlag, bool prbwindFlag,bool cis_flag, int cis_itvl,char* snpproblstName)
{
string logstr;
map<string, string> prb_snp;
map<string, string>::iterator iter;
eqtlInfo eqtlinfo;
cout<<endl<<"Reading QTL summary data..."<<endl;
if(eqtlFileName != NULL)
{
read_epifile(&eqtlinfo, string(eqtlFileName)+".epi");
epi_man(&eqtlinfo, problstName, genelistName, chr, prbchr, prbname, fromprbname, toprbname, prbWind, fromprbkb, toprbkb, prbwindFlag, genename);
read_esifile(&eqtlinfo, string(eqtlFileName)+".esi");
esi_man(&eqtlinfo, snplstName, chr, snpchr, snprs, fromsnprs, tosnprs, snpWind, fromsnpkb, tosnpkb, snpwindFlag, cis_flag, cis_itvl, prbname);
}
else throw ("Error: please input the eQTL summary information for the eQTL data files by the option --beqtl-summary.\n");
uint64_t epinum = eqtlinfo._probNum;
uint64_t esinum = eqtlinfo._snpNum;
vector<uint64_t> e_snp_idx;
vector<uint64_t> e_prb_idx;
for (int i = 0; i < eqtlinfo._esi_include.size(); i++) e_snp_idx.push_back(eqtlinfo._snp_name_map[eqtlinfo._esi_rs[eqtlinfo._esi_include[i]]]);
for (int i = 0; i < eqtlinfo._include.size(); i++) e_prb_idx.push_back(eqtlinfo._probe_name_map[eqtlinfo._epi_prbID[eqtlinfo._include[i]]]);
// get the effect sizes
vector<int> out_esi_id;
vector<int> out_epi_id;
vector<float> out_beta;
vector<float> out_se;
vector<double> out_pval;
FILE * fptr;
string besd_file = string(eqtlFileName)+".besd";
fptr = fopen(besd_file.c_str(),"rb");
fseek(fptr,0L,SEEK_SET);
uint32_t indicator=readuint32(fptr);
int infoLen=sizeof(uint32_t);
if(indicator==DENSE_FILE_TYPE_3) infoLen=RESERVEDUNITS*sizeof(int);
if(indicator!=DENSE_FILE_TYPE_1 && indicator!=DENSE_FILE_TYPE_3) {
cout << "ERROR: the BESD file is not in dense BESD format." << endl;
exit(EXIT_FAILURE);
}
float* tmp=(float*)malloc(sizeof(float)*esinum<<1);
for (int i = 0; i < eqtlinfo._include.size(); i++){
fseek(fptr,((e_prb_idx[i]*esinum)<<3)+infoLen, SEEK_SET);
fread(tmp, sizeof(float), esinum*2,fptr);
for (int j = 0; j< eqtlinfo._esi_include.size(); j++){
double beta=tmp[e_snp_idx[j]];
double se=tmp[e_snp_idx[j] + esinum];
if(fabs(se+9)<1e-6) continue;
double zsxz=beta/se;
double pxz=pchisq(zsxz*zsxz, 1);
if(pxz<=plookup){
out_esi_id.push_back(eqtlinfo._esi_include[j]);
out_epi_id.push_back(eqtlinfo._include[i]);
out_beta.push_back(beta);
out_se.push_back(se);
out_pval.push_back(pxz);
}
}
}
fclose(fptr);
string smrfile = string(outFileName)+".txt";
ofstream smr(smrfile.c_str());
if (!smr) throw ("Error: can not open the file " + smrfile + " to save!");
smr << "SNP" <<'\t'<< "Chr" <<'\t' << "BP" << '\t' << "A1" << '\t'<< "A2"<< '\t' <<"Freq"<<'\t'<< "Probe"<< '\t' << "Probe_Chr"<< '\t'<< "Probe_bp"<< '\t'<<"Gene"<<'\t'<<"Orientation"<<'\t'<<"b"<<'\t'<< "SE" << '\t'<<"p"<<'\n';
for (int i = 0;i <out_esi_id.size(); i++) {
smr<<eqtlinfo._esi_rs[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_chr[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_bp[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_allele1[out_esi_id[i]]<<'\t'<<eqtlinfo._esi_allele2[out_esi_id[i]]<<'\t'<<((eqtlinfo._esi_freq[out_esi_id[i]]+9>1e-6)?atos(eqtlinfo._esi_freq[out_esi_id[i]]):"NA")<<'\t'<<eqtlinfo._epi_prbID[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_chr[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_bp[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_gene[out_epi_id[i]]<<'\t'<<eqtlinfo._epi_orien[out_epi_id[i]]<<'\t'<<out_beta[i]<<'\t'<<out_se[i]<<'\t'<<out_pval[i]<< '\n';
}
smr.close();
cout<<"Extracted results of "<<out_esi_id.size()<<" SNPs have been saved in the file [" + smrfile + "]."<<endl;
}
void allele_check(bInfo* bdata, eqtlInfo* mdata, eqtlInfo* esdata, gwasData* gdata)
{
// get the common SNPs
vector<string> slctSNPs;
vector<string> b_snp_name;
vector<string> cmmnSNPs;
vector<int> bdId;
vector<int> gdId;
vector<int> edId;
vector<int> mdId;
cmmnSNPs.clear();
edId.clear();
string logstr="Checking the consistency of the alleles of each SNP between pairwise data sets (including the exposure QTL summary data, the mediation QTL summary data, the GWAS summary dataset and the LD reference data).\n";
cout<<logstr<<endl;
vector<string> bsnp(bdata->_include.size());
vector<string> gsnp(gdata->_include.size());
vector<string> msnp(mdata->_esi_include.size());
vector<string> essnp(esdata->_esi_include.size());
if(bdata->_include.size()< bdata->_snp_num || esdata->_esi_include.size()<esdata->_snpNum || mdata->_esi_include.size()<mdata->_snpNum )
{
#pragma omp parallel for
for(int i=0;i<bdata->_include.size();i++)
bsnp[i]=bdata->_snp_name[bdata->_include[i]];
#pragma omp parallel for
for(int i=0;i<gdata->_include.size();i++)
gsnp[i]=gdata->snpName[bdata->_include[i]];
#pragma omp parallel for
for(int i=0;i<mdata->_esi_include.size();i++)
msnp[i]=mdata->_esi_rs[mdata->_esi_include[i]];
#pragma omp parallel for
for(int i=0;i<esdata->_esi_include.size();i++)
essnp[i]=esdata->_esi_rs[esdata->_esi_include[i]];
match_only(bsnp, msnp, edId);
if(edId.empty()) throw("Error: no common SNPs between PLink data and mediation data.");
cmmnSNPs.resize(edId.size());
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
cmmnSNPs[i]=msnp[edId[i]];
edId.clear();
match_only(cmmnSNPs, gsnp, edId);
if(edId.empty()) throw("Error: no common SNPs found.");
cmmnSNPs.resize(edId.size());
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
cmmnSNPs[i]=gsnp[edId[i]];
edId.clear();
match_only(cmmnSNPs, essnp, edId);
if(edId.empty()) throw("Error: no common SNPs found.");
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
edId[i]=esdata->_esi_include[edId[i]];
slctSNPs.resize(edId.size());
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
slctSNPs[i]=essnp[edId[i]];
}else
{
match_only(bdata->_snp_name, mdata->_esi_rs, edId);
if(edId.empty()) throw("Error: no common SNPs between PLink data and mediation data.");
cmmnSNPs.resize(edId.size());
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
cmmnSNPs[i]=mdata->_esi_rs[edId[i]];
edId.clear();
match_only(cmmnSNPs, gdata->snpName, edId);
if(edId.empty()) throw("Error: no common SNPs found.");
cmmnSNPs.resize(edId.size());
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
cmmnSNPs[i]=gdata->snpName[edId[i]];
edId.clear();
match_only(cmmnSNPs, esdata->_esi_rs, edId);
if(edId.empty()) throw("Error: no common SNPs found.");
slctSNPs.resize(edId.size());
#pragma omp parallel for
for(int i=0;i<edId.size();i++)
slctSNPs[i]=esdata->_esi_rs[edId[i]];
}
//slctSNPs is in the order as bdata. so bdId is in increase order. edId and gdId may not.
//alleles check
match(slctSNPs, bdata->_snp_name, bdId);
match(slctSNPs, mdata->_esi_rs, mdId);
match(slctSNPs, gdata->snpName, gdId);
cmmnSNPs.clear();
bdata->_include.clear();
gdata->_include.clear();
mdata->_esi_include.clear();
esdata->_esi_include.clear();
double disp=0;
for (int i = 0; i<edId.size(); i++)
{
progress(i, disp, (int)edId.size());
string a1, a2, ga1, ga2, ea1, ea2, ma1, ma2;
a1 = bdata->_allele1[bdId[i]];
a2 = bdata->_allele2[bdId[i]];
ga1 = gdata->allele_1[gdId[i]];
ga2 = gdata->allele_2[gdId[i]];
ma1 = mdata->_esi_allele1[mdId[i]];
ma2 = mdata->_esi_allele2[mdId[i]];
ea1 = esdata->_esi_allele1[edId[i]];
ea2 = esdata->_esi_allele2[edId[i]];
// use the allele in eQTL summary data "esdata" as the reference allele. so we won't get the whole besd into memory
if(ea1 == a1 && ea2 == a2)
{
if( ea1 == ma1 && ea2 == ma2 && ea1 == ga1 && ea2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
}
else if(ea1 == ma2 && ea2 == ma1 && ea1 == ga1 && ea2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
string tmpch=mdata->_esi_allele1[mdId[i]];
mdata->_esi_allele1[mdId[i]] = mdata->_esi_allele2[mdId[i]];
mdata->_esi_allele2[mdId[i]] = tmpch;
if(mdata->_esi_freq[mdId[i]] >0) mdata->_esi_freq[mdId[i]] = 1 - mdata->_esi_freq[mdId[i]];
if(mdata->_val.size()>0)
{
int count=0;
for(int j=0;j<mdata->_rowid.size();j++)
{
if(mdata->_rowid[j]==mdId[i])
{
count++;
if(count & 1)
mdata->_val[j]=-1*mdata->_val[j];
}
}
}
else
{
int mid=mdId[i];
#pragma omp parallel for
for(int j=0;j<mdata->_include.size();j++)
if( fabs(mdata->_sexz[j][mid]+9) > 1e-6 )
mdata->_bxz[j][mid]=-1*mdata->_bxz[j][mid];
}
}
else if(ea1 == ma1 && ea2 == ma2 && ea1 == ga2 && ea2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
}
else if(ea1 == ma2 && ea2 == ma1 && ea1 == ga2 && ea2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
string tmpch=mdata->_esi_allele1[mdId[i]];
mdata->_esi_allele1[mdId[i]] = mdata->_esi_allele2[mdId[i]];
mdata->_esi_allele2[mdId[i]] = tmpch;
if(mdata->_esi_freq[mdId[i]] >0) mdata->_esi_freq[mdId[i]] = 1 - mdata->_esi_freq[mdId[i]];
if(mdata->_val.size()>0)
{
int count=0;
for(int j=0;j<mdata->_rowid.size();j++)
{
if(mdata->_rowid[j]==mdId[i])
{
count++;
if(count & 1)
mdata->_val[j]=-1*mdata->_val[j];
}
}
}
else
{
int mid=mdId[i];
#pragma omp parallel for
for(int j=0;j<mdata->_include.size();j++)
if( fabs(mdata->_sexz[j][mid]+9) > 1e-6 )
mdata->_bxz[j][mid]=-1*mdata->_bxz[j][mid];
}
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
}
}
else if(ea1 == a2 && ea2 == a1)
{
if( ea1 == ma1 && ea2 == ma2 && ea1 == ga1 && ea2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
string tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ea1 == ma2 && ea2 == ma1 && ea1 == ga1 && ea2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
string tmpch=mdata->_esi_allele1[mdId[i]];
mdata->_esi_allele1[mdId[i]] = mdata->_esi_allele2[mdId[i]];
mdata->_esi_allele2[mdId[i]] = tmpch;
if(mdata->_esi_freq[mdId[i]] >0) mdata->_esi_freq[mdId[i]] = 1 - mdata->_esi_freq[mdId[i]];
if(mdata->_val.size()>0)
{
int count=0;
for(int j=0;j<mdata->_rowid.size();j++)
{
if(mdata->_rowid[j]==mdId[i])
{
count++;
if(count & 1)
mdata->_val[j]=-1*mdata->_val[j];
}
}
}
else
{
int mid=mdId[i];
#pragma omp parallel for
for(int j=0;j<mdata->_include.size();j++)
if( fabs(mdata->_sexz[j][mid]+9) > 1e-6 )
mdata->_bxz[j][mid]=-1*mdata->_bxz[j][mid];
}
tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ea1 == ma1 && ea2 == ma2 && ea1 == ga2 && ea2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ea1 == ma2 && ea2 == ma1 && ea1 == ga2 && ea2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
string tmpch=mdata->_esi_allele1[mdId[i]];
mdata->_esi_allele1[mdId[i]] = mdata->_esi_allele2[mdId[i]];
mdata->_esi_allele2[mdId[i]] = tmpch;
if(mdata->_esi_freq[mdId[i]] >0) mdata->_esi_freq[mdId[i]] = 1 - mdata->_esi_freq[mdId[i]];
if(mdata->_val.size()>0)
{
int count=0;
for(int j=0;j<mdata->_rowid.size();j++)
{
if(mdata->_rowid[j]==mdId[i])
{
count++;
if(count & 1)
mdata->_val[j]=-1*mdata->_val[j];
}
}
}
else
{
int mid=mdId[i];
#pragma omp parallel for
for(int j=0;j<mdata->_include.size();j++)
if( fabs(mdata->_sexz[j][mid]+9) > 1e-6 )
mdata->_bxz[j][mid]=-1*mdata->_bxz[j][mid];
}
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
}
}
logstr= "\n" + atos(bdata->_include.size())+" SNPs are included after allele check. ";
cout<<logstr<<endl;
// only update _snp_name_map which would be used in read bed file.
map<string, int> id_map_buf(bdata->_snp_name_map);
for(int i=0; i<bdata->_include.size(); i++) id_map_buf.erase(bdata->_snp_name[bdata->_include[i]]);
map<string, int>::iterator iter;
for(iter=id_map_buf.begin(); iter!=id_map_buf.end(); iter++) bdata->_snp_name_map.erase(iter->first);
}
void allele_check(bInfo* bdata, eqtlInfo* mdata, eqtlInfo* esdata, gwasData* gdata, bool incmp_expo)
{
// get the common SNPs
vector<string> slctSNPs;
vector<string> b_snp_name;
vector<string> cmmnSNPs;
vector<int> bdId;
vector<int> gdId;
vector<int> edId;
vector<int> mdId;
cmmnSNPs.clear();
mdId.clear();
string logstr="Checking the consistency of the alleles of each SNP between pairwise data sets (including the exposure QTL summary data, the mediation QTL summary data, the GWAS summary dataset and the LD reference data).\n";
cout<<logstr<<endl;
vector<string> bsnp(bdata->_include.size());
vector<string> gsnp(gdata->_include.size());
vector<string> msnp(mdata->_esi_include.size());
vector<string> essnp(esdata->_esi_include.size());
if(bdata->_include.size()< bdata->_snp_num || esdata->_esi_include.size()<esdata->_snpNum || mdata->_esi_include.size()<mdata->_snpNum )
{
#pragma omp parallel for
for(int i=0;i<bdata->_include.size();i++)
bsnp[i]=bdata->_snp_name[bdata->_include[i]];
#pragma omp parallel for
for(int i=0;i<gdata->_include.size();i++)
gsnp[i]=gdata->snpName[bdata->_include[i]];
#pragma omp parallel for
for(int i=0;i<mdata->_esi_include.size();i++)
msnp[i]=mdata->_esi_rs[mdata->_esi_include[i]];
match_only(bsnp, gsnp, mdId);
if(mdId.empty()) throw("Error: no common SNPs between PLink data and GWAS data.");
slctSNPs.resize(mdId.size());
#pragma omp parallel for
for(int i=0;i<mdId.size();i++)
slctSNPs[i]=gsnp[mdId[i]];
mdId.clear();
match_only(slctSNPs, msnp, mdId);
if(mdId.empty()) throw("Error: no common SNPs found.");
slctSNPs.resize(mdId.size());
#pragma omp parallel for
for(int i=0;i<mdId.size();i++)
slctSNPs[i]=msnp[mdId[i]];
if (!incmp_expo){
#pragma omp parallel for
for(int i=0;i<esdata->_esi_include.size();i++)
essnp[i]=esdata->_esi_rs[esdata->_esi_include[i]];
mdId.clear();
match_only(slctSNPs, essnp, mdId);
if(mdId.empty()) throw("Error: no common SNPs found.");
slctSNPs.resize(mdId.size());
#pragma omp parallel for
for(int i=0;i<mdId.size();i++)
slctSNPs[i]=essnp[mdId[i]];
match(slctSNPs, mdata->_esi_rs, mdId);
}
}else
{
match_only(bdata->_snp_name, gdata->snpName, mdId);
if(mdId.empty()) throw("Error: no common SNPs between PLink data and GWAS data.");
slctSNPs.resize(mdId.size());
#pragma omp parallel for
for(int i=0;i<mdId.size();i++)
slctSNPs[i]=gdata->snpName[mdId[i]];
mdId.clear();
match_only(slctSNPs, mdata->_esi_rs, mdId);
if(mdId.empty()) throw("Error: no common SNPs found.");
slctSNPs.resize(mdId.size());
#pragma omp parallel for
for(int i=0;i<mdId.size();i++)
slctSNPs[i]=mdata->_esi_rs[mdId[i]];
if (!incmp_expo){
mdId.clear();
match_only(slctSNPs, esdata->_esi_rs, mdId);
if(mdId.empty()) throw("Error: no common SNPs found.");
slctSNPs.resize(mdId.size());
#pragma omp parallel for
for(int i=0;i<mdId.size();i++)
slctSNPs[i]=esdata->_esi_rs[mdId[i]];
match(slctSNPs, mdata->_esi_rs, mdId);
}
}
logstr= atos(slctSNPs.size())+" SNPs are included after allele check based on SNP ID. ";
cout<<logstr<<endl;
//slctSNPs is in the order as bdata. so bdId is in increase order. edId and gdId may not.
//alleles check
match(slctSNPs, bdata->_snp_name, bdId);
match(slctSNPs, gdata->snpName, gdId);
//match(slctSNPs, mdata->_esi_rs, mdId);
match(slctSNPs, esdata->_esi_rs, edId);
cmmnSNPs.clear();
bdata->_include.clear();
gdata->_include.clear();
mdata->_esi_include.clear();
esdata->_esi_include.clear();
double disp=0;
for (int i = 0; i<mdId.size(); i++)
{
progress(i, disp, (int)mdId.size());
string a1, a2, ga1, ga2, ea1, ea2, ma1, ma2;
a1 = bdata->_allele1[bdId[i]];
a2 = bdata->_allele2[bdId[i]];
ga1 = gdata->allele_1[gdId[i]];
ga2 = gdata->allele_2[gdId[i]];
ma1 = mdata->_esi_allele1[mdId[i]];
ma2 = mdata->_esi_allele2[mdId[i]];
if (edId[i] > -9){
ea1 = esdata->_esi_allele1[edId[i]];
ea2 = esdata->_esi_allele2[edId[i]];
} else {
ea1 = a1;
ea2 = a2;
}
// use the allele in mediator summary data "mdata" as the reference allele. so we won't get the whole besd into memory
if(ma1 == a1 && ma2 == a2)
{
if( ma1 == ea1 && ma2 == ea2 && ma1 == ga1 && ma2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
}
else if(ma1 == ea2 && ma2 == ea1 && ma1 == ga1 && ma2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
if (edId[i] > -9){
string tmpch=esdata->_esi_allele1[edId[i]];
esdata->_esi_allele1[edId[i]] = esdata->_esi_allele2[edId[i]];
esdata->_esi_allele2[edId[i]] = tmpch;
if(esdata->_esi_freq[edId[i]] >0) esdata->_esi_freq[edId[i]] = 1 - esdata->_esi_freq[edId[i]];
if(esdata->_val.size()>0)
{
int count=0;
for(int j=0;j<esdata->_rowid.size();j++)
{
if(esdata->_rowid[j]== edId[i])
{
count++;
if(count & 1)
esdata->_val[j]=-1*esdata->_val[j];
}
}
}
else
{
int eid=edId[i];
#pragma omp parallel for
for(int j=0;j<esdata->_include.size();j++)
if(fabs(esdata->_sexz[j][eid]+9) > 1e-6 )
esdata->_bxz[j][eid]=-1*esdata->_bxz[j][eid];
}
}
}
else if(ma1 == ea1 && ma2 == ea2 && ma1 == ga2 && ma2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
}
else if(ma1 == ea2 && ma2 == ea1 && ma1 == ga2 && ma2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
if (edId[i] > -9){
string tmpch=esdata->_esi_allele1[edId[i]];
esdata->_esi_allele1[edId[i]] = esdata->_esi_allele2[edId[i]];
esdata->_esi_allele2[edId[i]] = tmpch;
if(esdata->_esi_freq[edId[i]] >0) esdata->_esi_freq[edId[i]] = 1 - esdata->_esi_freq[edId[i]];
if(esdata->_val.size()>0)
{
int count=0;
for(int j=0;j<esdata->_rowid.size();j++)
{
if(esdata->_rowid[j]==edId[i])
{
count++;
if(count & 1)
esdata->_val[j]=-1*esdata->_val[j];
}
}
}
else
{
int eid=edId[i];
#pragma omp parallel for
for(int j=0;j<esdata->_include.size();j++)
if(fabs(esdata->_sexz[j][eid]+9) > 1e-6 )
esdata->_bxz[j][eid]=-1*esdata->_bxz[j][eid];
}
}
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
}
}
else if(ma1 == a2 && ma2 == a1)
{
if(ma1 == ea1 && ma2 == ea2 && ma1 == ga1 && ma2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
string tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ma1 == ea2 && ma2 == ea1 && ma1 == ga1 && ma2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
if (edId[i] > -9){
string tmpch=esdata->_esi_allele1[edId[i]];
esdata->_esi_allele1[edId[i]] = esdata->_esi_allele2[edId[i]];
esdata->_esi_allele2[edId[i]] = tmpch;
if(esdata->_esi_freq[edId[i]] >0) esdata->_esi_freq[edId[i]] = 1 - esdata->_esi_freq[edId[i]];
if(esdata->_val.size()>0)
{
int count=0;
for(int j=0;j<esdata->_rowid.size();j++)
{
if(esdata->_rowid[j]==edId[i])
{
count++;
if(count & 1)
esdata->_val[j]=-1*esdata->_val[j];
}
}
}
else
{
int eid=edId[i];
#pragma omp parallel for
for(int j=0;j<esdata->_include.size();j++)
if( fabs(esdata->_sexz[j][eid]+9) > 1e-6 )
esdata->_bxz[j][eid]=-1*esdata->_bxz[j][eid];
}
}
string tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ma1 == ea1 && ma2 == ea2 && ma1 == ga2 && ma2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ma1 == ea2 && ma2 == ea1 && ma1 == ga2 && ma2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
mdata->_esi_include.push_back(mdId[i]);
esdata->_esi_include.push_back(edId[i]);
if (edId[i] > -9){
string tmpch=esdata->_esi_allele1[edId[i]];
esdata->_esi_allele1[edId[i]] = esdata->_esi_allele2[edId[i]];
esdata->_esi_allele2[edId[i]] = tmpch;
if(esdata->_esi_freq[edId[i]] >0) esdata->_esi_freq[edId[i]] = 1 - esdata->_esi_freq[edId[i]];
if(esdata->_val.size()>0)
{
int count=0;
for(int j=0;j<esdata->_rowid.size();j++)
{
if(esdata->_rowid[j]==edId[i])
{
count++;
if(count & 1)
esdata->_val[j]=-1*esdata->_val[j];
}
}
}
else
{
int eid=edId[i];
#pragma omp parallel for
for(int j=0;j<esdata->_include.size();j++)
if( fabs(esdata->_sexz[j][eid]+9) > 1e-6 )
esdata->_bxz[j][eid]=-1*esdata->_bxz[j][eid];
}
}
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
}
}
logstr= "\n" + atos(bdata->_include.size())+" SNPs are included after allele check. ";
cout<<logstr<<endl;
// update _snp_name_map which will be used in read bed file.
map<string, int> id_map_buf(bdata->_snp_name_map);
for(int i=0; i<bdata->_include.size(); i++) id_map_buf.erase(bdata->_snp_name[bdata->_include[i]]);
map<string, int>::iterator iter;
for(iter=id_map_buf.begin(); iter!=id_map_buf.end(); iter++) bdata->_snp_name_map.erase(iter->first);
}
void allele_check(bInfo* bdata, gwasData* gdata, gwasData* gdata2)
{
// get the common SNPs
vector<string> slctSNPs;
vector<string> b_snp_name;
vector<string> cmmnSNPs;
vector<int> bdId;
vector<int> gdId;
vector<int> edId;
cmmnSNPs.clear();
edId.clear();
string logstr="Checking the consistency of the alleles of each SNP between pairwise data sets (including the exposure GWAS summary data, the outcome GWAS summary data and the LD reference data).";
cout<<logstr<<endl;
vector<string> bsnp;
if(bdata->_include.size()< bdata->_snp_num)
{
for(int i=0;i<bdata->_include.size();i++) bsnp.push_back(bdata->_snp_name[bdata->_include[i]]);
StrFunc::match_only(bsnp, gdata->snpName, edId);
if(edId.empty()) throw("Error: no SNPs in common between reference data and exposure GWAS data.");
for(int i=0;i<edId.size();i++) cmmnSNPs.push_back(gdata->snpName[edId[i]]);
StrFunc::match_only(cmmnSNPs, gdata2->snpName, edId);
if(edId.empty()) throw("Error: no SNPs in common.");
for(int i=0;i<edId.size();i++) slctSNPs.push_back(gdata2->snpName[edId[i]]);
}else
{
StrFunc::match_only(bdata->_snp_name, gdata->snpName, edId);
if(edId.empty()) throw("Error: no SNPs in common between reference data and GWAS data.");
for(int i=0;i<edId.size();i++) cmmnSNPs.push_back(gdata->snpName[edId[i]]);
edId.clear();
StrFunc::match_only(cmmnSNPs, gdata2->snpName, edId);
if(edId.empty()) throw("Error: no SNPs in common.");
for(int i=0;i<edId.size();i++) slctSNPs.push_back(gdata2->snpName[edId[i]]);
}
//slctSNPs is in the order as bdata. so bdId is in increase order. edId and gdId may not.
//logstr=itos(edId.size())+" SNPs are included after rsID check. ";
//cout<<logstr<<endl;
//alleles check
StrFunc::match(slctSNPs, bdata->_snp_name, bdId);
StrFunc::match(slctSNPs, gdata->snpName, gdId);
cmmnSNPs.clear();
bdata->_include.clear();
gdata->_include.clear();
gdata2->_include.clear();
for (int i = 0; i<edId.size(); i++)
{
string a1, a2, ga1, ga2, ea1, ea2;
a1 = bdata->_allele1[bdId[i]];
a2 = bdata->_allele2[bdId[i]];
ga1 = gdata->allele_1[gdId[i]];
ga2 = gdata->allele_2[gdId[i]];
ea1 = gdata2->allele_1[edId[i]];
ea2 = gdata2->allele_2[edId[i]];
// use the allele in outcome GWAS summary data as the reference allele
if(ea1 == a1 && ea2 == a2)
{
if( ea1 == ga1 && ea2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
gdata2->_include.push_back(edId[i]);
}
else if(ea1 == ga2 && ea2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
gdata2->_include.push_back(edId[i]);
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
}
}
else if(ea1 == a2 && ea2 == a1)
{
if( ea1 == ga1 && ea2 == ga2)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
gdata2->_include.push_back(edId[i]);
string tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
else if(ea1 == ga2 && ea2 == ga1)
{
bdata->_include.push_back(bdId[i]);
gdata->_include.push_back(gdId[i]);
gdata2->_include.push_back(edId[i]);
gdata->byz[gdId[i]]=-gdata->byz[gdId[i]];
string tmpch=gdata->allele_1[gdId[i]];
gdata->allele_1[gdId[i]] = gdata->allele_2[gdId[i]];
gdata->allele_2[gdId[i]] = tmpch;
if(gdata->freq[gdId[i]]>0) gdata->freq[gdId[i]] = 1 - gdata->freq[gdId[i]];
tmpch=bdata->_ref_A[bdId[i]];
bdata->_ref_A[bdId[i]]=bdata->_other_A[bdId[i]];
bdata->_other_A[bdId[i]]=tmpch;
}
}
}
logstr=itos(bdata->_include.size())+" SNPs are included after allele checking. ";
cout<<logstr<<endl;
// only update _snp_name_map which would be used in read bed file.
map<string, int> id_map_buf(bdata->_snp_name_map);
for(int i=0; i<bdata->_include.size(); i++) id_map_buf.erase(bdata->_snp_name[bdata->_include[i]]);
map<string, int>::iterator iter;
for(iter=id_map_buf.begin(); iter!=id_map_buf.end(); iter++) bdata->_snp_name_map.erase(iter->first);
}
double freq_check(bInfo* bdata, eqtlInfo* mdata, eqtlInfo* esdata, gwasData* gdata, double &freqthresh, double &percenthresh)
{
cout << "Checking the consistency of allele frequency of each SNP between pairwise data sets (including the GWAS summary data, the eQTL summary data, the mediation data and the LD reference data).\n" << endl;
bool success=true;
long failcount=0, snpnum=bdata->_include.size();
vector<int> pasbid, pasgid, paseid, pasmid;
string fname=string(outFileName) + ".snp_failed_freq_ck.list";
FILE* tmpfile=fopen(fname.c_str(), "w");
if (!(tmpfile)) {
printf("Error: Failed to open file %s.\n",fname.c_str());
exit(EXIT_FAILURE);
}
string tmpstr = "SNP\tAllele\tReferencePanel\tGWAS\teQTL\tmdata\n";
fputs(tmpstr.c_str(),tmpfile);
for(int i=0;i<bdata->_include.size();i++)
{
double bfreq=bdata->_mu[bdata->_include[i]]/2;
double gfreq=gdata->freq[gdata->_include[i]];
double efreq;
if (esdata->_esi_include[i] > -9){
efreq=esdata->_esi_freq[esdata->_esi_include[i]];
} else {
efreq = bdata->_mu[bdata->_include[i]]/2;
}
double mfreq;
if (mdata->_esi_include[i] > -9){
mfreq=mdata->_esi_freq[mdata->_esi_include[i]];
} else {
mfreq = bdata->_mu[bdata->_include[i]]/2;
}
if(gfreq<0 && efreq>0 && mfreq>0)
{
if(fabs(bfreq-efreq)>freqthresh || fabs(bfreq-mfreq)>freqthresh || fabs(efreq-mfreq)>freqthresh)
{
failcount++;
tmpstr=mdata->_esi_rs[mdata->_esi_include[i]] + '\t' + mdata->_esi_allele1[mdata->_esi_include[i]]+ '\t' + atos(bfreq) + '\t' + atos(gfreq) + '\t' + atos(efreq) + '\t' + atos(mfreq) + '\n';
fputs(tmpstr.c_str(),tmpfile);
}
else
{
pasbid.push_back(bdata->_include[i]);
pasgid.push_back(gdata->_include[i]);
paseid.push_back(esdata->_esi_include[i]);
pasmid.push_back(mdata->_esi_include[i]);
}
}
else if(gfreq>0 && efreq<0 && mfreq>0)
{
if(fabs(bfreq-gfreq)>freqthresh || fabs(bfreq-mfreq)>freqthresh || fabs(gfreq-mfreq)>freqthresh)
{
failcount++;
tmpstr=mdata->_esi_rs[mdata->_esi_include[i]] + '\t' + mdata->_esi_allele1[mdata->_esi_include[i]]+ '\t' + atos(bfreq) + '\t' + atos(gfreq) + '\t' + atos(efreq) + '\t' + atos(mfreq) + '\n';
fputs(tmpstr.c_str(),tmpfile);
}
else
{
pasbid.push_back(bdata->_include[i]);
pasgid.push_back(gdata->_include[i]);
paseid.push_back(esdata->_esi_include[i]);
pasmid.push_back(mdata->_esi_include[i]);
}
}
else if(gfreq>0 && efreq>0 && mfreq<0)
{
if(fabs(bfreq-gfreq)>freqthresh || fabs(bfreq-efreq)>freqthresh || fabs(gfreq-efreq)>freqthresh)
{
failcount++;
tmpstr=mdata->_esi_rs[mdata->_esi_include[i]] + '\t' + mdata->_esi_allele1[mdata->_esi_include[i]]+ '\t' + atos(bfreq) + '\t' + atos(gfreq) + '\t' + atos(efreq) + '\t' + atos(mfreq) + '\n';
fputs(tmpstr.c_str(),tmpfile);