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-b-4813 Constructing ScanVcfParam object. VCF contains: 7,190,058 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: - 7,190,052 rows - 7,170,346 unique variants - 10,583 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 55 seconds. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 10,000 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 93 seconds. Inferred genome build: GRCH37 Checking SNP RSIDs. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ieu-b-4813/logs/snp_missing_rs.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. Sorting coordinates with 'data.table'. Writing in tabular format ==> /rds/general/project/neurogenomics-lab/ephemeral/MAGMA_Files_Public/data/GWAS_munged/ieu-b-4813/logs/snp_multi_colon.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. 25 SNP IDs appear to be made up of chr:bp, these will be replaced by their SNP ID 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-b-4813/logs/snp_not_found_from_bp_chr.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 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 7,170,340 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 161 seconds. 521,599 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-b-4813/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 7,162,724 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 229 seconds. Checking for correct direction of A1 (reference) and A2 (alternative allele). There are 39 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-b-4813/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 15 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. 177,966 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-b-4813/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-b-4813/ieu-b-4813.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: - 6,984,719 rows (97.1% of original 7,190,052 rows) - 6,984,719 unique variants - 10,314 genome-wide significant variants (P<5e-8) - 22 chromosomes Done munging in 28.824 minutes. Successfully finished preparing sumstats file, preview: Reading header. SNP CHR BP A1 A2 END FILTER BETA LP SE N 1: rs58013264 1 797440 T C 797440 PASS 0.0061 0.0421055 0.0523 58335 2: rs10900604 1 798400 A G 798400 PASS -0.0111 0.0989233 0.0428 59725 3: rs11240777 1 798959 G A 798959 PASS 0.0029 0.0243385 0.0419 61885 4: rs61768212 1 801467 G C 801467 PASS 0.0124 0.0895357 0.0525 57957 5: rs7526310 1 804759 C T 804759 PASS 0.0177 0.1326500 0.0526 57957 P Z 1: 0.9076000 0.11606626 2: 0.7963000 -0.25813856 3: 0.9454999 0.06835891 4: 0.8137000 0.23565554 5: 0.7368006 0.33609312