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-GCST004296 Constructing ScanVcfParam object. VCF contains: 10,719,646 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: - 10,455,114 rows - 10,455,033 unique variants - 1,296 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 47 seconds. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 10,000 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 61 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 10,455,033 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 204 seconds. 55,096 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-GCST004296/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 10,405,344 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 238 seconds. Checking for correct direction of A1 (reference) and A2 (alternative allele). There are 417 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-GCST004296/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 272 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. 79 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-GCST004296/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. 8 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-GCST004296/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. 286,526 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-GCST004296/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-GCST004296/ebi-a-GCST004296.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: - 10,118,398 rows (96.8% of original 10,455,114 rows) - 10,118,398 unique variants - 1,260 genome-wide significant variants (P<5e-8) - 22 chromosomes Done munging in 34.603 minutes. Successfully finished preparing sumstats file, preview: Reading header. SNP CHR BP A1 A2 END FILTER REVERSECOMPLEMENTEDALLELES BETA 1: rs58108140 1 10583 G A 10583 PASS FALSE 0.0640 2: rs806731 1 30923 G T 30923 PASS FALSE -0.0371 3: rs116400033 1 51479 T A 51479 PASS FALSE -0.0210 4: rs2691277 1 52238 T G 52238 PASS FALSE 0.0214 5: rs146477069 1 54421 A G 54421 PASS FALSE -0.2109 LP SE P Z 1: 0.5622490 0.0585 0.2740003 1.0938967 2: 0.3635120 0.0474 0.4330001 -0.7840682 3: 0.1565800 0.0540 0.6973005 -0.3889670 4: 0.0736061 0.1090 0.8441000 0.1966518 5: 0.5777390 0.1890 0.2643997 -1.1160524