Loading required namespace: GenomicFiles Using local VCF. File already tabix-indexed. Finding empty VCF columns based on first 10,000 rows. 1 sample detected: ieu-a-976 Constructing ScanVcfParam object. VCF contains: 2,610,160 variant(s) x 1 sample(s) Reading VCF file: multi-threaded (4 threads) Renaming ID as SNP. VCF file has -log10 P-values; these will be converted to unadjusted p-values in the 'P' column. No INFO (SI) column detected. Standardising column headers. First line of summary statistics file: SNP chr BP end REF ALT FILTER ES LP SE SS P Summary statistics report: - 2,548,807 rows - 2,548,807 unique variants - 119 genome-wide significant variants (P<5e-8) - 22 chromosomes Checking for multi-GWAS. Checking for multiple RSIDs on one row. Inferring genome build. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 10,000 SNPs using BSgenome::snpsById... Loading required package: BiocGenerics Attaching package: ‘BiocGenerics’ The following objects are masked from ‘package:stats’: IQR, mad, sd, var, xtabs The following objects are masked from ‘package:base’: anyDuplicated, aperm, append, as.data.frame, basename, cbind, colnames, dirname, do.call, duplicated, eval, evalq, Filter, Find, get, grep, grepl, intersect, is.unsorted, lapply, Map, mapply, match, mget, order, paste, pmax, pmax.int, pmin, pmin.int, Position, rank, rbind, Reduce, rownames, sapply, setdiff, sort, table, tapply, union, unique, unsplit, which.max, which.min Loading required package: S4Vectors Loading required package: stats4 Attaching package: ‘S4Vectors’ The following objects are masked from ‘package:base’: expand.grid, I, unname BSgenome::snpsById done in 28 seconds. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 10,000 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 52 seconds. Inferred genome build: GRCH37 Checking SNP RSIDs. Checking for merged allele column. Checking A1 is uppercase Checking A2 is uppercase Checking for incorrect base-pair positions Ensuring all SNPs are on the reference genome. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 2,548,807 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 58 seconds. 10,061 SNPs are not on the reference genome. These will be corrected from the reference genome. Loading SNPlocs data. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ieu-a-976/logs/snp_not_found_from_chr_bp.tsv Writing uncompressed instead of gzipped to enable tabix indexing. Converting full summary stats file to tabix format for fast querying... Reading header. Ensuring file is bgzipped. Tabix-indexing file. Removing temporary .tsv file. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 2,538,948 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 54 seconds. Checking for correct direction of A1 (reference) and A2 (alternative allele). There are 30 SNPs where neither A1 nor A2 match the reference genome. These will be removed. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ieu-a-976/logs/alleles_dont_match_ref_gen.tsv Writing uncompressed instead of gzipped to enable tabix indexing. Converting full summary stats file to tabix format for fast querying... Reading header. Ensuring file is bgzipped. Tabix-indexing file. Removing temporary .tsv file. There are 23 SNPs where A1 doesn't match the reference genome. These will be flipped with their effect columns. Reordering so first three column headers are SNP, CHR and BP in this order. Reordering so the fourth and fifth columns are A1 and A2. Checking for missing data. Checking for duplicate columns. Ensuring that the N column is all integers. The sumstats N column is not all integers, this could effect downstream analysis. These will be converted to integers. Checking for duplicate SNPs from SNP ID. Checking for SNPs with duplicated base-pair positions. INFO column not available. Skipping INFO score filtering step. Filtering SNPs, ensuring SE>0. Ensuring all SNPs have N<5 std dev above mean. Checking for bi-allelic SNPs. 66,585 SNPs are non-biallelic. These will be removed. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ieu-a-976/logs/snp_bi_allelic.tsv Writing uncompressed instead of gzipped to enable tabix indexing. Converting full summary stats file to tabix format for fast querying... Reading header. Ensuring file is bgzipped. Tabix-indexing file. Removing temporary .tsv file. Computing Z-score from P using formula: `sign(BETA)*sqrt(stats::qchisq(P,1,lower=FALSE)` N already exists within sumstats_dt. Sorting coordinates with 'data.table'. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ieu-a-976/ieu-a-976.tsv Writing uncompressed instead of gzipped to enable tabix indexing. Converting full summary stats file to tabix format for fast querying... Reading header. Ensuring file is bgzipped. Tabix-indexing file. Removing temporary .tsv file. Summary statistics report: - 2,472,333 rows (97% of original 2,548,807 rows) - 2,472,333 unique variants - 116 genome-wide significant variants (P<5e-8) - 22 chromosomes Done munging in 6.922 minutes. Successfully finished preparing sumstats file, preview: Reading header. SNP CHR BP A1 A2 END FILTER BETA LP SE N 1: rs11497407 1 568527 G A 568527 PASS -1.652350 1.0292300 0.985141 64171 2: rs12565286 1 721290 G C 721290 PASS 0.103115 0.3421420 0.137968 64171 3: rs11804171 1 723819 T A 723819 PASS 0.103188 0.3426360 0.137907 64171 4: rs2977670 1 723891 G C 723891 PASS -0.103205 0.3428610 0.137858 64171 5: rs2977656 1 729948 C T 729948 PASS -0.233512 0.0906895 0.979371 64171 P Z 1: 0.09349104 -1.6772631 2: 0.45483932 0.7473715 3: 0.45432224 0.7482287 4: 0.45408693 -0.7486189 5: 0.81154106 -0.2384384