Loading required namespace: GenomicFiles Using local VCF. File already tabix-indexed. Finding empty VCF columns based on first 10,000 rows. Dropping 1 duplicate column(s). 1 sample detected: ieu-b-98 Constructing ScanVcfParam object. VCF contains: 7,506,712 variant(s) x 1 sample(s) Reading VCF file: multi-threaded (4 threads) Dropping 1 duplicate column(s). Dropping 1 duplicate column(s). Dropping 1 duplicate column(s). Dropping 1 duplicate column(s). Renaming ID as SNP. VCF file has -log10 P-values; these will be converted to unadjusted p-values in the 'P' column. Renaming SI column as INFO. Formatting INFO column. Standardising column headers. First line of summary statistics file: SNP chr BP end REF ALT FILTER AF ES LP NC SE INFO SS P Summary statistics report: - 7,292,112 rows - 7,271,502 unique variants - 0 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 73 seconds. Loading SNPlocs data. Loading reference genome data. Preprocessing RSIDs. Validating RSIDs of 10,000 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 60 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-98/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-98/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. 907 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-98/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 7,270,656 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 63 seconds. 544,954 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-98/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 7,256,350 SNPs using BSgenome::snpsById... BSgenome::snpsById done in 88 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-98/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 18 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. Filtering SNPs based on INFO score. 1,919,296 SNPs are below the INFO threshold of 0.9 and 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-98/logs/info_filter.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. Filtering SNPs, ensuring SE>0. Ensuring all SNPs have N<5 std dev above mean. Checking for bi-allelic SNPs. 135,593 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-98/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. 1,165,839 SNPs (22.4%) have FRQ values > 0.5. Conventionally the FRQ column is intended to show the minor/effect allele frequency. The FRQ column was mapped from one of the following from the inputted summary statistics file: FRQ, EAF, FREQUENCY, FRQ_U, F_U, MAF, FREQ, FREQ_TESTED_ALLELE, FRQ_TESTED_ALLELE, FREQ_EFFECT_ALLELE, FRQ_EFFECT_ALLELE, EFFECT_ALLELE_FREQUENCY, EFFECT_ALLELE_FREQ, EFFECT_ALLELE_FRQ, A1FREQ, A1FRQ, A2FREQ, A2FRQ, ALLELE_FREQUENCY, ALLELE_FREQ, ALLELE_FRQ, AF, MINOR_AF, EFFECT_AF, A2_AF, EFF_AF, ALT_AF, ALTERNATIVE_AF, INC_AF, A_2_AF, TESTED_AF, AF1, ALLELEFREQ, ALT_FREQ, EAF_HRC, EFFECTALLELEFREQ, FREQ.A1.1000G.EUR, FREQ.A1.ESP.EUR, FREQ.ALLELE1.HAPMAPCEU, FREQ.B, FREQ1, FREQ1.HAPMAP, FREQ_EUROPEAN_1000GENOMES, FREQ_HAPMAP, FREQ_TESTED_ALLELE_IN_HRS, FRQ_A1, FRQ_U_113154, FRQ_U_31358, FRQ_U_344901, FRQ_U_43456, POOLED_ALT_AF, AF_ALT, AF.ALT, AF-ALT, ALT.AF, ALT-AF, A2.AF, A2-AF, AF.EFF, AF_EFF, AF_EFF As frq_is_maf=TRUE, the FRQ column will not be renamed. If the FRQ values were intended to represent major allele frequency, set frq_is_maf=FALSE to rename the column as MAJOR_ALLELE_FRQ and differentiate it from minor/effect allele frequency. 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-98/ieu-b-98.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: - 5,201,422 rows (71.3% of original 7,292,112 rows) - 5,201,422 unique variants - 0 genome-wide significant variants (P<5e-8) - 22 chromosomes Done munging in 15.726 minutes. Successfully finished preparing sumstats file, preview: Reading header. SNP CHR BP A1 A2 END FILTER FRQ BETA LP N_CAS 1: rs3094315 1 752566 G A 752566 PASS 0.783 -0.051 0.14152300 205 2: rs3131972 1 752721 A G 752721 PASS 0.758 -0.043 0.12378200 205 3: rs112563271 1 770377 A T 770377 PASS 0.013 0.015 0.00988323 205 4: rs10900604 1 798400 A G 798400 PASS 0.282 0.054 0.17152300 205 5: rs11240777 1 798959 G A 798959 PASS 0.282 0.053 0.16825800 205 SE INFO N P Z 1: 0.143 1.000 932 0.7218999 -0.3559207 2: 0.136 1.000 932 0.7520003 -0.3160029 3: 0.525 1.000 932 0.9775000 0.0282033 4: 0.127 0.993 932 0.6737162 0.4210532 5: 0.127 1.000 932 0.6788003 0.4141008