LD_Check

## LD check

library("ieugwasr")
library("TwoSampleMR")
library("readxl")
input <- read_excel("D:/ld check list.xlsx",sheet = "Sheet1")

for (i in 1:nrow(input)){
  print(i)
  
  c <- NULL  
  d <- input[i,]
  
  region <- paste0(d[1,2], ":", d[1,4], "-", d[1,5])
  dat <- ieugwasr::associations(region,"ebi-a-GCST90012110")  
  
  exposure_dat <-format_data(dat, type = "exposure", header = TRUE, 
                             snp_col = "rsid", beta_col = "beta",
                             se_col = "se", eaf_col = "eaf", effect_allele_col = "ea",
                             other_allele_col = "nea", pval_col = "p", samplesize_col = "n",)
    
  ## T2D 
  outcome_dat <- NULL
  attempts <- 0
  while(attempts<=10){
    try(
      outcome_dat <- read_outcome_data(
        snps = exposure_dat$SNP,
        filename = "D:/Zheng meeting/single cell project/outcome data/DIAMANTE-EUR.sumstat.txt",                 
        sep = " ",
        snp_col = "rsID",
        beta_col = "Fixed-effects_beta",
        se_col = "Fixed-effects_SE",
        effect_allele_col = "effect_allele",
        other_allele_col = "other_allele",
        eaf_col = "effect_allele_frequency",
        pval_col = "Fixed-effects_p-value")
    )
    if(is.null(outcome_dat)){
      attempts<-attempts+1}
    else{
      break
    }
  }
  outcome_dat$outcome <- "T2D" 
    
  data <- harmonise_data(exposure_dat, outcome_dat, action=1)
  
  try(data <- data[order(data$pval.outcome),]) 
  try(data <- data[data$pval.outcome<1E-3,])
  try(if(nrow(data)>=500){data <- data[1:499,] })
  #str(data)
  
  if (nrow(data)!=0){
    rsid <- as.character(unlist(d[1,6]))
    snp <- append(as.character(unlist(data$SNP)), rsid)
    
    a <- NULL
    attempts <- 0
    while(attempts<=10){    
      try(a <- ld_matrix(snps=snp))  
      if(is.null(a)){
        attempts<-attempts+1}
      else{
        break
      }
    }
    
    if(is.null(nrow(a))==TRUE){
      c <- as.data.frame(cbind(as.character(unlist(d[1,6])), as.character(unlist(d[1,1])),rsid, 1 ) )
    } else {
      col.index <- which(grepl(rsid,colnames(a)))
      b <- (a[,col.index])^2
      b <- b[order(b)]
      b <- b[(length(b)-1)] 
      c <- as.data.frame(cbind(as.character(unlist(d[1,6])),as.character(unlist(d[1,1])), names(b), as.character(unlist(b))) )
    }
    
  } else {
    c <- as.data.frame(cbind(as.character(unlist(d[1,6])), as.character(unlist(d[1,1])),"NA","NA" ) ) 
  } 
  
  result_file <- paste0("./ld-check/",as.character(unlist(d[1,6])),".",as.character(unlist(d[1,1])),".ldcheck.txt")
  if (exists("c")==TRUE){ write.table(c,file=result_file,sep="\t",col.names=F,row.names=F,quote=F)}
  
}