Loading required namespace: GenomicFiles Using local VCF. File already tabix-indexed. Finding empty VCF columns based on first 10,000 rows. 1 sample detected: EBI-a-GCST004137 Constructing ScanVcfParam object. VCF contains: 11,094,833 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 ReverseComplementedAlleles ES LP SE P Summary statistics report: - 11,071,379 rows - 9,200,703 unique variants - 1,505 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 9,998 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 81 seconds. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 9,998 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 71 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 9,200,703 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 395 seconds. 1,928,937 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/ebi-a-GCST004137/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 9,148,132 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 358 seconds. Checking for correct direction of A1 (reference) and A2 (alternative allele). There are 563 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/ebi-a-GCST004137/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 345 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. Checking for duplicate SNPs from SNP ID. 1,840,510 RSIDs are duplicated in the sumstats file. These duplicates will be removed Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ebi-a-GCST004137/logs/dup_snp_id.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. Checking for SNPs with duplicated base-pair positions. 16 base-pair positions are duplicated in the sumstats file. These duplicates will be removed. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ebi-a-GCST004137/logs/dup_base_pair_position.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. 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. 253,511 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/ebi-a-GCST004137/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)` Warning: When method is an integer, must be >0. 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/ebi-a-GCST004137/ebi-a-GCST004137.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: - 8,894,169 rows (80.3% of original 11,071,379 rows) - 8,894,169 unique variants - 1,425 genome-wide significant variants (P<5e-8) - 22 chromosomes Done munging in 52.873 minutes. Successfully finished preparing sumstats file, preview: Reading header. SNP CHR BP A1 A2 END FILTER REVERSECOMPLEMENTEDALLELES BETA 1: rs114420996 1 58814 G A 58814 PASS FALSE 0.0024 2: rs62637815 1 59040 T C 59040 PASS FALSE 0.0106 3: rs76735897 1 61987 A G 61987 PASS FALSE 0.0043 4: rs77573425 1 61989 G C 61989 PASS FALSE -0.0001 5: rs80011619 1 63671 G A 63671 PASS FALSE 0.0085 LP SE P Z 1: 0.04143610 0.0209 0.9090000 0.114299934 2: 0.18151000 0.0239 0.6584003 0.442122906 3: 0.12912800 0.0132 0.7428002 0.328147449 4: 0.00217692 0.0132 0.9950000 -0.006266614 5: 0.20176400 0.0177 0.6283997 0.483980448