From 2eb890d9920b45083e28d84ee1298afbd3ff897f Mon Sep 17 00:00:00 2001 From: AlexandrePelletier Date: Wed, 11 Mar 2026 18:53:05 -0400 Subject: [PATCH 1/2] APOE indep cs ROSMAP neuropatho --- .../staging/APOE_code/APOE_cs_neuropatho.R | 250 ++++++++++++++++++ 1 file changed, 250 insertions(+) create mode 100644 main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R diff --git a/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R b/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R new file mode 100644 index 00000000..5bfa409b --- /dev/null +++ b/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R @@ -0,0 +1,250 @@ +source('../../utils/r_utils.R') +out<-'main_text/5_AD_xQTL_genes_cis_trans/staging/APOE/' +dir.create(out) +#APOE4 independant APOE cs are associated with neuropatho in ROSMAP ? + +res_indep_cs<-readRDS('main_text/5_AD_xQTL_genes_cis_trans/staging/APOE/xqtl_only_APOE_all_cohorts_independent_sets_after_imputation_no_sQTL_only.rds') +length(res_indep_cs$variant_id) +indep_cs<-rbindlist(lapply(names(res_indep_cs$variant_id),function(n)data.table(cs_name=n,variant_id=res_indep_cs$variant_id[[n]], + gwas_source=res_indep_cs$ad_gwas[[which(names(res_indep_cs$variant_id)==n)]], + outcome=res_indep_cs$outcome[[n]]))) +indep_cs[,cs_id:=paste0('set_',str_extract(cs_name,'[0-9]+$'))] +indep_cs[,chr:=seqid(variant_id)] +indep_cs[,pos:=pos(variant_id)] +indep_cs[,variant_id2:=str_replace_all(variant_id,':','_')|>str_replace('_',':')] +#extract genotype for those CS +fwrite(indep_cs[order(chr,pos)][,.(variant_id2)],fp(out,'apoe4_indep_snps.tsv'),sep = '\t',col.names=FALSE) + +plink_file<-'/projectnb/tcwlab-adsp/member/adpelle1/projects/fungen-xqtl/ref-data/ROSMAP/ROSMAP_NIA_geno/ROSMAP_NIA_WGS.leftnorm.bcftools_qc.plink_qc' + +cmd=paste('plink --bfile',tools::file_path_sans_ext(plink_file), + '--extract',fp(out,'apoe4_indep_snps.tsv'), + '--recode vcf', + '--out',fp(out,'ROSMAP_geno_apoe4_indep_snps')) +# cmd=paste('plink --bfile',tools::file_path_sans_ext(plink_file), +# '--extract range',fp(out,'AD_snps_5pbwin.tsv'), +# '--recode vcf', +# '--out',fp(out,basename(plink_file)|>tools::file_path_sans_ext()|>paste0('.donors_apoecs.only'))) +system(cmd) +#add snps infos to donors mtd +donors_apoecs<-fread(fp(out,'ROSMAP_geno_apoe4_indep_snps.vcf')) +dim(donors_apoecs)#216 1162 + +donors_apoecs<-melt(donors_apoecs[,-c(6:9)], + id.vars = c('#CHROM','POS','ID','REF','ALT'), + variable.name = 'IID',value.name = 'geno') +donors_apoecs[,dose:=str_count(geno,'1')] + +donors_apoecs[,variant_id2:=ID] +donors_apoecs<-merge(donors_apoecs,indep_cs,by='variant_id2') + +clin<-fread('../../../acandib/APOE_Ab/Metadata_Files/ROSMAP_clinical.csv') +bios<-fread('../../../acandib/APOE_Ab/Metadata_Files/ROSMAP_biospecimen_metadata.csv') +clinw<-merge(clin,bios[assay=='wholeGenomeSeq'][,.(individualID,specimenID)],by='individualID') +complete<-fread('../../../acandib/APOE_Ab/Metadata_Files/ROSMAP_xqtl_complete_samples_covariates_sex_death_pmi_study.csv') +setnames(complete,'sample_id','specimenID') +clinw<-merge(clinw[,-c('age_death','pmi','msex')],complete,by='specimenID') + +donors_apoecs[,specimenID:=str_remove(IID,'0_')] + +donors_apoecs<-merge(donors_apoecs,clinw,by='specimenID') + +unique(donors_apoecs$individualID)|>length()#1116 +unique(donors_apoecs$individualID)|>length()#OK + +#add neuropatho +neuropath<-fread('main_text/5_AD_xQTL_genes_cis_trans/staging/APOE/dataset_707_basic_02-10-2022.n3711.clean.plink.n2409.28FEB2022.txt') +dim(neuropath)#266 +neuropathf<-neuropath[,.SD,.SDcols = c('projid','amyloid_sqrt','tangles_sqrt','cogng_path_slope','plaq_d','plaq_n_sqrt','nft_sqrt','tdp_cs_6reg','tdp_dn_6reg','tdp_st4','caa_4gp','caa_neo4')] +donors_apoecs<-merge(donors_apoecs,neuropathf,all.x = TRUE,by='projid') + +#neuropatho analysis coreecting for APOE4 /2 gentoyep + + +donors_apoecs[,apoe4_dose:=str_count(apoe_genotype,'4')] +donors_apoecs[,apoe2_dose:=str_count(apoe_genotype,'2')] + +donors_apoecs[,cogdx_binary:=ifelse(cogdx%in%c(4,5),'AD',ifelse(cogdx%in%1:3,'No AD',NA))] +donors_apoecs[,cogdx_merge:=ifelse(cogdx%in%c(4,5),'AD',ifelse(cogdx%in%2:3,'MCI',ifelse(cogdx==1,'NL',NA)))] +donors_apoecs[,cogdx_merge:=factor(cogdx_merge,levels = c('NL','MCI','AD'))] +donors_apoecs[cogdx!=6,cogdx_mergenum:=ifelse(cogdx_merge=='MCI',2,ifelse(cogdx_merge=='AD',3,1))] + +donors_apoecs[,age_first_ad_dx_num:=ifelse(age_first_ad_dx=='90+',91,as.numeric(age_first_ad_dx))] +donors_apoecs[,other_dementia:=cogdx==6] +donors_apoecs[,other_CI:=cogdx%in%c(3,5)] +donors_apoecs[cogdx%in%c(1,4,5),ADvsNL:=cogdx%in%c(4,5)] +donors_apoecs[cogdx%in%c(1,2,3),MCIvsNL:=cogdx%in%c(2,3)] + +donors_apoecs[,ceradsc_pos:=-ceradsc] +donors_apoecs[,braaksc06:=ifelse(braaksc==0,1,ifelse(braaksc==6,5,braaksc))] +donors_apoecs[,age_first_ad_dx_num:=ifelse(age_first_ad_dx=='90+',91,as.numeric(age_first_ad_dx))] +donors_apoecs[(cogdx_binary=='AD'),age_first_clinad_dx:=age_first_ad_dx_num] +donors_apoecs[(cogdx_binary=='AD'),cts_mmse30_lv_clinad:=cts_mmse30_lv] + +donors_apoecs[,age_at_visit_num:=ifelse(age_at_visit_max=='90+', + 91,as.numeric(age_at_visit_max))] +donors_apoecs[dcfdx_lv!=6,dcfdx_lv_no6:=dcfdx_lv] + +donors_apoecs[,apoe2_r:=cor(dose,apoe2_dose,use = 'pairwise.complete.obs'),by='ID'] +donors_apoecs[,apoe4_r:=cor(dose,apoe4_dose,use = 'pairwise.complete.obs'),by='ID'] + +fwrite(donors_apoecs,fp(out,'ROSMAP_geno_apoecs_adpathology.csv.gz')) + + +covs_lin<-c('ceradsc_pos','braaksc06', + 'dcfdx_lv_no6','cts_mmse30_lv','age_death', + 'cogdx_mergenum','apoe4_dose','apoe2_dose', + 'cts_mmse30_lv_clinad','age_first_ad_dx_num', + 'age_first_clinad_dx','amyloid_sqrt','tangles_sqrt', + 'cogng_path_slope', + 'plaq_d','plaq_n_sqrt','nft_sqrt','tdp_cs_6reg','tdp_dn_6reg','tdp_st4','caa_4gp','caa_neo4' +) + + +covs_logis<-c('MCIvsNL','ADvsNL') + +apoecs_clin<-rbindlist(lapply(covs_lin,function(c){ + message(c) + if(!c%in%c('age_death','cts_mmse30_lv','cts_mmse30_lv_clinad','age_first_ad_dx_num','age_first_clinad_dx','cogng_path_slope')){ + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + }else if(c%in%c('cts_mmse30_lv','cts_mmse30_lv_clinad')){ + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_at_visit_num+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + }else{ + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + } + +})) +apoecs_clin[,zscore:=`t value`] +apoecs_clin[,pval:=`Pr(>|t|)`] + +apoecs_clogit<-rbindlist(lapply(covs_logis,function(c){ + message(c) + donors_apoecs[,summary(glm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose+apoe2_dose,family = binomial))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + +})) +apoecs_clogit[,zscore:=`z value`] +apoecs_clogit[,pval:=`Pr(>|z|)`] + +apoecs_clin<-rbind(apoecs_clin,apoecs_clogit,fill=TRUE) + +apoecs_clin<-merge(apoecs_clin,indep_cs,by='variant_id2') +apoecs_clin[,padj:=p.adjust(pval,n = length(unique(indep_cs$cs_name))),by=c('cov','variant_id2')] +apoecs_clin[padj<0.05] + + +apoecs_clin[!cov%in%c('apoe4_dose','apoe2_dose')][padj<0.05] + +apoecs_clin[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')]$cs_id |>unique()|>length()#3/19 + +fwrite(apoecs_clin,fp(out,'res_lm_apoecs_adpathology_apoe4_2_correction.csv.gz')) + + +unique(apoecs_clin[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')][order(cs_id,cov,padj)][,.(cs_id,cov,padj,gwas_source,outcome)],by=c('cs_id','cov')) + +# +# cs_id cov padj +# +# 1: set_27 caa_4gp 0.004708944 +# 2: set_27 caa_neo4 0.007830511 +# 3: set_27 tdp_st4 0.042915291 +# 4: set_31 age_first_ad_dx_num 0.020960086 +# 5: set_57 tangles_sqrt 0.003434581 +# gwas_source +# +# 1: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 2: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 3: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 4: AD_Bellenguez +# 5: AD_Bellenguez; AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 + + +#set27 is the caa set of Fujita et al? +apoecs_clin[pos(variant_id2)==44946027]#yes + + + +#APOE4 only +apoecs_clin2<-rbindlist(lapply(covs_lin,function(c){ + message(c) + if(!c%in%c('age_death','cts_mmse30_lv','cts_mmse30_lv_clinad','age_first_ad_dx_num','age_first_clinad_dx','cogng_path_slope')){ + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + }else if(c%in%c('cts_mmse30_lv','cts_mmse30_lv_clinad')){ + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_at_visit_num+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + }else{ + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + } + +})) +apoecs_clin2[,zscore:=`t value`] +apoecs_clin2[,pval:=`Pr(>|t|)`] + +apoecs_clogit2<-rbindlist(lapply(covs_logis,function(c){ + message(c) + donors_apoecs[,summary(glm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose,family = binomial))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + +})) +apoecs_clogit2[,zscore:=`z value`] +apoecs_clogit2[,pval:=`Pr(>|z|)`] + +apoecs_clin2<-rbind(apoecs_clin2,apoecs_clogit2,fill=TRUE) + +apoecs_clin2<-merge(apoecs_clin2,indep_cs,by='variant_id2') +apoecs_clin2[,padj:=p.adjust(pval,n = length(unique(indep_cs$cs_name))),by=c('cov','variant_id2')] +apoecs_clin2[padj<0.05] + + +apoecs_clin2[!cov%in%c('apoe4_dose','apoe2_dose')][padj<0.05] + +apoecs_clin2[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')]$cs_id |>unique()|>length()#4/19 + +fwrite(apoecs_clin2,fp(out,'res_lm_apoecs_adpathology_apoe4_correction.csv.gz')) + + +unique(apoecs_clin2[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')][order(cs_id,cov,padj)][,.(cs_id,cov,variant_id2,padj,gwas_source,outcome)],by=c('cs_id','cov')) +# cs_id cov variant_id2 padj +# +# 1: set_26 age_first_ad_dx_num chr19:44918487_G_T 0.046608400 +# 2: set_27 caa_4gp chr19:44954310_T_C 0.002833505 +# 3: set_27 caa_neo4 chr19:44954310_T_C 0.004877779 +# 4: set_27 tdp_st4 chr19:44999110_TAAAA_TAA 0.042966548 +# 5: set_31 age_first_ad_dx_num chr19:45114770_ACCC_AC 0.020474889 +# 6: set_57 tangles_sqrt chr19:44840322_G_A 0.020962988 +# gwas_source +# +# 1: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 +# 2: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 3: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 4: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 5: AD_Bellenguez +# 6: AD_Bellenguez; AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 +# outcome +# +# 1: AC_DeJager_eQTL_ENSG00000130208; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130208; ROSMAP_AC_ENSG00000130208; ROSMAP_DLPFC_ENSG00000130208 +# 2: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 +# 3: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 +# 4: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 +# 5: AC_DeJager_eQTL_ENSG00000189114; DLPFC_DeJager_eQTL_ENSG00000189114; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000189114; PCC_DeJager_eQTL_ENSG00000189114; ROSMAP_AC_ENSG00000189114; ROSMAP_DLPFC_ENSG00000189114; ROSMAP_PCC_ENSG00000189114 +# 6: Ast_10_Kellis_eQTL_ENSG00000160007 + + Ast_10_Kellis_eQTL_ENSG00000160007 +#set26 is APOE2? + +apoecs_clin2[cs_id=='set_26'&pos(variant_id2)==44908822]#no + +donors_apoecs[variant_id2=='chr19:44918487_G_T']$apoe2_r[1]#-0.21 +donors_apoecs[variant_id2=='chr19:44918487_G_T']$apoe4_r[1]#-0.23 + +#CCL: We can validate 3 of the 19 independant variants sets independently explaining one neuropathology after adjusted for APOE4 and 2 dose (along with Sex, education and age covariates), +#and 4/19 sets once we do not adjust for APOE4. These results is for FDR<0.05, using BH correction with n=19 tests + +# breakdown of the neuropathology associated sets: +# set27 is the APOE Mic eQTL that have previously been found associated with cerebral amyloid angiopathy in Fujita et al, and we are able to recapitulate this association. The 3 others sets are set_26, 31 and 57, +# respectively eQTL of APOC1 (in several brain regions and STARNET Mac), BLOC1S3( in several brain regions ), both explaining age at AD onset, and ARHGAP35 (in Ast.10 specifically), explaining Tau tangle level. From a7ea2d8914dd1c36566c27dccdd893836bc54132 Mon Sep 17 00:00:00 2001 From: AlexandrePelletier Date: Thu, 12 Mar 2026 14:21:30 -0400 Subject: [PATCH 2/2] clean script --- .../staging/APOE_code/APOE_cs_neuropatho.R | 167 ++++++++++-------- 1 file changed, 90 insertions(+), 77 deletions(-) diff --git a/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R b/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R index 5bfa409b..f6bf1af5 100644 --- a/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R +++ b/main_text/5_AD_xQTL_genes_cis_trans/staging/APOE_code/APOE_cs_neuropatho.R @@ -7,11 +7,12 @@ res_indep_cs<-readRDS('main_text/5_AD_xQTL_genes_cis_trans/staging/APOE/xqtl_onl length(res_indep_cs$variant_id) indep_cs<-rbindlist(lapply(names(res_indep_cs$variant_id),function(n)data.table(cs_name=n,variant_id=res_indep_cs$variant_id[[n]], gwas_source=res_indep_cs$ad_gwas[[which(names(res_indep_cs$variant_id)==n)]], - outcome=res_indep_cs$outcome[[n]]))) + molecular_outcome=res_indep_cs$outcome[[n]]))) indep_cs[,cs_id:=paste0('set_',str_extract(cs_name,'[0-9]+$'))] indep_cs[,chr:=seqid(variant_id)] indep_cs[,pos:=pos(variant_id)] indep_cs[,variant_id2:=str_replace_all(variant_id,':','_')|>str_replace('_',':')] + #extract genotype for those CS fwrite(indep_cs[order(chr,pos)][,.(variant_id2)],fp(out,'apoe4_indep_snps.tsv'),sep = '\t',col.names=FALSE) @@ -21,27 +22,27 @@ cmd=paste('plink --bfile',tools::file_path_sans_ext(plink_file), '--extract',fp(out,'apoe4_indep_snps.tsv'), '--recode vcf', '--out',fp(out,'ROSMAP_geno_apoe4_indep_snps')) -# cmd=paste('plink --bfile',tools::file_path_sans_ext(plink_file), -# '--extract range',fp(out,'AD_snps_5pbwin.tsv'), -# '--recode vcf', -# '--out',fp(out,basename(plink_file)|>tools::file_path_sans_ext()|>paste0('.donors_apoecs.only'))) + system(cmd) -#add snps infos to donors mtd + +#format the genotype donors_apoecs<-fread(fp(out,'ROSMAP_geno_apoe4_indep_snps.vcf')) dim(donors_apoecs)#216 1162 donors_apoecs<-melt(donors_apoecs[,-c(6:9)], - id.vars = c('#CHROM','POS','ID','REF','ALT'), - variable.name = 'IID',value.name = 'geno') + id.vars = c('#CHROM','POS','ID','REF','ALT'), + variable.name = 'IID',value.name = 'geno') donors_apoecs[,dose:=str_count(geno,'1')] donors_apoecs[,variant_id2:=ID] donors_apoecs<-merge(donors_apoecs,indep_cs,by='variant_id2') -clin<-fread('../../../acandib/APOE_Ab/Metadata_Files/ROSMAP_clinical.csv') -bios<-fread('../../../acandib/APOE_Ab/Metadata_Files/ROSMAP_biospecimen_metadata.csv') + +#add the clinical covariates +clin<-fread('/projectnb/tcwlab/ShareSpace/ROSMAP_Neuropatho/ROSMAP_clinical.csv') +bios<-fread('/projectnb/tcwlab/ShareSpace/ROSMAP_Neuropatho/ROSMAP_biospecimen_metadata.csv') #for WGS samples ID - IndividualID link clinw<-merge(clin,bios[assay=='wholeGenomeSeq'][,.(individualID,specimenID)],by='individualID') -complete<-fread('../../../acandib/APOE_Ab/Metadata_Files/ROSMAP_xqtl_complete_samples_covariates_sex_death_pmi_study.csv') +complete<-fread('/projectnb/tcwlab/ShareSpace/ROSMAP_Neuropatho/ROSMAP_xqtl_complete_samples_covariates_sex_death_pmi_study.csv') setnames(complete,'sample_id','specimenID') clinw<-merge(clinw[,-c('age_death','pmi','msex')],complete,by='specimenID') @@ -50,22 +51,24 @@ donors_apoecs[,specimenID:=str_remove(IID,'0_')] donors_apoecs<-merge(donors_apoecs,clinw,by='specimenID') unique(donors_apoecs$individualID)|>length()#1116 -unique(donors_apoecs$individualID)|>length()#OK -#add neuropatho -neuropath<-fread('main_text/5_AD_xQTL_genes_cis_trans/staging/APOE/dataset_707_basic_02-10-2022.n3711.clean.plink.n2409.28FEB2022.txt') -dim(neuropath)#266 +#add neuropatho covs +#we test only a subset of the covariates +neuropath<-fread('/projectnb/tcwlab/ShareSpace/ROSMAP_Neuropatho/dataset_707_basic_02-10-2022.n3711.clean.plink.n2409.28FEB2022.txt') +dim(neuropath) neuropathf<-neuropath[,.SD,.SDcols = c('projid','amyloid_sqrt','tangles_sqrt','cogng_path_slope','plaq_d','plaq_n_sqrt','nft_sqrt','tdp_cs_6reg','tdp_dn_6reg','tdp_st4','caa_4gp','caa_neo4')] -donors_apoecs<-merge(donors_apoecs,neuropathf,all.x = TRUE,by='projid') - -#neuropatho analysis coreecting for APOE4 /2 gentoyep +#add those phenotype to the genotypes +donors_apoecs<-merge(donors_apoecs,neuropathf,all.x = TRUE,by='projid') +#neuropatho analysis correcting for APOE4 /2 gentoyep donors_apoecs[,apoe4_dose:=str_count(apoe_genotype,'4')] donors_apoecs[,apoe2_dose:=str_count(apoe_genotype,'2')] -donors_apoecs[,cogdx_binary:=ifelse(cogdx%in%c(4,5),'AD',ifelse(cogdx%in%1:3,'No AD',NA))] -donors_apoecs[,cogdx_merge:=ifelse(cogdx%in%c(4,5),'AD',ifelse(cogdx%in%2:3,'MCI',ifelse(cogdx==1,'NL',NA)))] +#prep/reformat the phenotypes +donors_apoecs[,cogdx_binary:=ifelse(cogdx%in%c(4,5),'AD',ifelse(cogdx%in%1:3,'No AD',NA))] #binarize the cognitive status + +donors_apoecs[,cogdx_merge:=ifelse(cogdx%in%c(4,5),'AD',ifelse(cogdx%in%2:3,'MCI',ifelse(cogdx==1,'NL',NA)))] # three level cognitive status donors_apoecs[,cogdx_merge:=factor(cogdx_merge,levels = c('NL','MCI','AD'))] donors_apoecs[cogdx!=6,cogdx_mergenum:=ifelse(cogdx_merge=='MCI',2,ifelse(cogdx_merge=='AD',3,1))] @@ -77,6 +80,7 @@ donors_apoecs[cogdx%in%c(1,2,3),MCIvsNL:=cogdx%in%c(2,3)] donors_apoecs[,ceradsc_pos:=-ceradsc] donors_apoecs[,braaksc06:=ifelse(braaksc==0,1,ifelse(braaksc==6,5,braaksc))] + donors_apoecs[,age_first_ad_dx_num:=ifelse(age_first_ad_dx=='90+',91,as.numeric(age_first_ad_dx))] donors_apoecs[(cogdx_binary=='AD'),age_first_clinad_dx:=age_first_ad_dx_num] donors_apoecs[(cogdx_binary=='AD'),cts_mmse30_lv_clinad:=cts_mmse30_lv] @@ -91,6 +95,7 @@ donors_apoecs[,apoe4_r:=cor(dose,apoe4_dose,use = 'pairwise.complete.obs'),by='I fwrite(donors_apoecs,fp(out,'ROSMAP_geno_apoecs_adpathology.csv.gz')) +#outcome to test with Lm covs_lin<-c('ceradsc_pos','braaksc06', 'dcfdx_lv_no6','cts_mmse30_lv','age_death', 'cogdx_mergenum','apoe4_dose','apoe2_dose', @@ -100,30 +105,38 @@ covs_lin<-c('ceradsc_pos','braaksc06', 'plaq_d','plaq_n_sqrt','nft_sqrt','tdp_cs_6reg','tdp_dn_6reg','tdp_st4','caa_4gp','caa_neo4' ) - +#outcome to test with logistic regression covs_logis<-c('MCIvsNL','ADvsNL') -apoecs_clin<-rbindlist(lapply(covs_lin,function(c){ - message(c) - if(!c%in%c('age_death','cts_mmse30_lv','cts_mmse30_lv_clinad','age_first_ad_dx_num','age_first_clinad_dx','cogng_path_slope')){ - donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] - }else if(c%in%c('cts_mmse30_lv','cts_mmse30_lv_clinad')){ +#outcome that are measured before death +atlastvisit=c('cts_mmse30_lv','cts_mmse30_lv_clinad')#outcome that need to be adjusted for age at last visit + +beforedeath<-c('age_death','cts_mmse30_lv','cts_mmse30_lv_clinad','age_first_ad_dx_num','age_first_clinad_dx','cogng_path_slope') + +#Adjusting for both APOE4 and APOE2#### +apoecs_clin<-rbindlist(lapply(covs_lin,function(outc){ + message(outc) + if(outc%in%atlastvisit){ donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_at_visit_num+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] - }else{ + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] + + }else if(outc%in%beforedeath){ donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] + }else{ + + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose+apoe2_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] } })) apoecs_clin[,zscore:=`t value`] apoecs_clin[,pval:=`Pr(>|t|)`] -apoecs_clogit<-rbindlist(lapply(covs_logis,function(c){ - message(c) +apoecs_clogit<-rbindlist(lapply(covs_logis,function(outc){ + message(outc) donors_apoecs[,summary(glm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose+apoe2_dose,family = binomial))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] })) apoecs_clogit[,zscore:=`z value`] @@ -132,34 +145,33 @@ apoecs_clogit[,pval:=`Pr(>|z|)`] apoecs_clin<-rbind(apoecs_clin,apoecs_clogit,fill=TRUE) apoecs_clin<-merge(apoecs_clin,indep_cs,by='variant_id2') -apoecs_clin[,padj:=p.adjust(pval,n = length(unique(indep_cs$cs_name))),by=c('cov','variant_id2')] +apoecs_clin[,padj:=p.adjust(pval,n = length(unique(indep_cs$cs_name))),by=c('outcome','variant_id2')] apoecs_clin[padj<0.05] -apoecs_clin[!cov%in%c('apoe4_dose','apoe2_dose')][padj<0.05] +apoecs_clin[!outcome%in%c('apoe4_dose','apoe2_dose')][padj<0.05] -apoecs_clin[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')]$cs_id |>unique()|>length()#3/19 +apoecs_clin[padj<0.05][!outcome%in%c('apoe4_dose','apoe2_dose')]$cs_id |>unique()|>length()#3/19 fwrite(apoecs_clin,fp(out,'res_lm_apoecs_adpathology_apoe4_2_correction.csv.gz')) -unique(apoecs_clin[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')][order(cs_id,cov,padj)][,.(cs_id,cov,padj,gwas_source,outcome)],by=c('cs_id','cov')) +unique(apoecs_clin[padj<0.05][!outcome%in%c('apoe4_dose','apoe2_dose')][order(cs_id,outcome,padj)][,.(cs_id,outcome,padj,gwas_source,molecular_outcome)],by=c('cs_id','outcome')) -# -# cs_id cov padj -# -# 1: set_27 caa_4gp 0.004708944 -# 2: set_27 caa_neo4 0.007830511 -# 3: set_27 tdp_st4 0.042915291 -# 4: set_31 age_first_ad_dx_num 0.020960086 -# 5: set_57 tangles_sqrt 0.003434581 -# gwas_source -# -# 1: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 -# 2: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 -# 3: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 -# 4: AD_Bellenguez -# 5: AD_Bellenguez; AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 +# cs_id outcome padj gwas_source +# +# 1: set_27 caa_4gp 0.004708944 AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 2: set_27 caa_neo4 0.007830511 AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 3: set_27 tdp_st4 0.042915291 AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 +# 4: set_31 age_first_ad_dx_num 0.020960086 AD_Bellenguez +# 5: set_57 tangles_sqrt 0.003434581 AD_Bellenguez; AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 +# molecular_outcome +# +# 1: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 +# 2: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 +# 3: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 +# 4: AC_DeJager_eQTL_ENSG00000189114; DLPFC_DeJager_eQTL_ENSG00000189114; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000189114; PCC_DeJager_eQTL_ENSG00000189114; ROSMAP_AC_ENSG00000189114; ROSMAP_DLPFC_ENSG00000189114; ROSMAP_PCC_ENSG00000189114 +# 5: Ast_10_Kellis_eQTL_ENSG00000160007 #set27 is the caa set of Fujita et al? @@ -167,28 +179,30 @@ apoecs_clin[pos(variant_id2)==44946027]#yes -#APOE4 only -apoecs_clin2<-rbindlist(lapply(covs_lin,function(c){ - message(c) - if(!c%in%c('age_death','cts_mmse30_lv','cts_mmse30_lv_clinad','age_first_ad_dx_num','age_first_clinad_dx','cogng_path_slope')){ - donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] - }else if(c%in%c('cts_mmse30_lv','cts_mmse30_lv_clinad')){ +#adjusting for APOE4 only#### +apoecs_clin2<-rbindlist(lapply(covs_lin,function(outc){ + message(outc) + if(outc%in%atlastvisit){ donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_at_visit_num+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] - }else{ + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] + + }else if(outc%in%beforedeath){ donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] + }else{ + + donors_apoecs[,summary(lm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose))$coefficients|>data.table(keep.rownames = 'cov'), + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] } })) apoecs_clin2[,zscore:=`t value`] apoecs_clin2[,pval:=`Pr(>|t|)`] -apoecs_clogit2<-rbindlist(lapply(covs_logis,function(c){ - message(c) +apoecs_clogit2<-rbindlist(lapply(covs_logis,function(outc){ + message(outc) donors_apoecs[,summary(glm(unlist(.SD)~dose+msex+educ+age_death+apoe4_dose,family = binomial))$coefficients|>data.table(keep.rownames = 'cov'), - by='variant_id2',.SDcols=c][cov=='dose'][,cov:=c] + by='variant_id2',.SDcols=outc][cov=='dose'][,outcome:=outc] })) apoecs_clogit2[,zscore:=`z value`] @@ -197,43 +211,42 @@ apoecs_clogit2[,pval:=`Pr(>|z|)`] apoecs_clin2<-rbind(apoecs_clin2,apoecs_clogit2,fill=TRUE) apoecs_clin2<-merge(apoecs_clin2,indep_cs,by='variant_id2') -apoecs_clin2[,padj:=p.adjust(pval,n = length(unique(indep_cs$cs_name))),by=c('cov','variant_id2')] +apoecs_clin2[,padj:=p.adjust(pval,n = length(unique(indep_cs$cs_name))),by=c('outcome','variant_id2')] apoecs_clin2[padj<0.05] -apoecs_clin2[!cov%in%c('apoe4_dose','apoe2_dose')][padj<0.05] +apoecs_clin2[!outcome%in%c('apoe4_dose','apoe2_dose')][padj<0.05] -apoecs_clin2[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')]$cs_id |>unique()|>length()#4/19 +apoecs_clin2[padj<0.05][!outcome%in%c('apoe4_dose','apoe2_dose')]$cs_id |>unique()|>length()#3/19 fwrite(apoecs_clin2,fp(out,'res_lm_apoecs_adpathology_apoe4_correction.csv.gz')) -unique(apoecs_clin2[padj<0.05][!cov%in%c('apoe4_dose','apoe2_dose')][order(cs_id,cov,padj)][,.(cs_id,cov,variant_id2,padj,gwas_source,outcome)],by=c('cs_id','cov')) -# cs_id cov variant_id2 padj -# +unique(apoecs_clin2[padj<0.05][!outcome%in%c('apoe4_dose','apoe2_dose')][order(cs_id,cov,padj)][,.(cs_id,outcome,variant_id2,padj,gwas_source,molecular_outcome)],by=c('cs_id','outcome')) +# cs_id outcome variant_id2 padj +# # 1: set_26 age_first_ad_dx_num chr19:44918487_G_T 0.046608400 # 2: set_27 caa_4gp chr19:44954310_T_C 0.002833505 # 3: set_27 caa_neo4 chr19:44954310_T_C 0.004877779 # 4: set_27 tdp_st4 chr19:44999110_TAAAA_TAA 0.042966548 # 5: set_31 age_first_ad_dx_num chr19:45114770_ACCC_AC 0.020474889 # 6: set_57 tangles_sqrt chr19:44840322_G_A 0.020962988 -# gwas_source -# -# 1: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 +# gwas_source +# +# 1: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 # 2: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 # 3: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 # 4: AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021; AD_Wightman_ExcludingUKBand23andME_2021 # 5: AD_Bellenguez # 6: AD_Bellenguez; AD_Kunkle_Stage1_2019; AD_Wightman_Full_2021; AD_Wightman_Excluding23andMe_2021 -# outcome -# +# molecular_outcome +# # 1: AC_DeJager_eQTL_ENSG00000130208; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130208; ROSMAP_AC_ENSG00000130208; ROSMAP_DLPFC_ENSG00000130208 # 2: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 # 3: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 # 4: AC_DeJager_eQTL_ENSG00000224916; AC_DeJager_eQTL_ENSG00000234906; BM_10_MSBB_eQTL_ENSG00000104853; Metabrain_Basalganglia_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cerebellum_chr19_41840000_47960000_ENSG00000234906; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000104853; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000234906; Mic_DeJager_eQTL_ENSG00000130208; Mic_DeJager_eQTL_ENSG00000130203; Mic_mega_eQTL_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000130208; STARNET_eQTL_Mac_ENSG00000130203; STARNET_eQTL_Mac_ENSG00000267467; STARNET_eQTL_Mac_ENSG00000224916; STARNET_eQTL_Mac_ENSG00000234906; DeJager_Mic_ENSG00000130203; Kellis_Mic_ENSG00000130203; DeJager_Mic_ENSG00000130208; Kellis_Mic_ENSG00000130208 # 5: AC_DeJager_eQTL_ENSG00000189114; DLPFC_DeJager_eQTL_ENSG00000189114; Metabrain_Cortex_chr19_41840000_47960000_ENSG00000189114; PCC_DeJager_eQTL_ENSG00000189114; ROSMAP_AC_ENSG00000189114; ROSMAP_DLPFC_ENSG00000189114; ROSMAP_PCC_ENSG00000189114 # 6: Ast_10_Kellis_eQTL_ENSG00000160007 - Ast_10_Kellis_eQTL_ENSG00000160007 #set26 is APOE2?