This example dataset was obtained from the UK BioBank (https://www.ukbiobank.ac.uk/).

It is used for illustration purpose with fake ID, respecting otherwise available UKBB data.

The participants.tsv shows how to indicate what genetic information is available.

This description was created 16 Feb 2018.

Calls

=====

The genotype calls are in binary PLINK format (.bed, .bim, .fam) see https://www.cog-genomics.org/plink/1.9/formats for details of the formats.

The BIM file determines the order of markers in the calls and all of the other genotype data sets. The SNP_id is the rsid where it is available or the Affymetrix_SNP_id otherwise. The positions are in GRCh37 coordinates.

The FAM file determines the order of samples in the calls and all of the other genotype data sets. The FAM file includes 'Batch' in the Phenotype field (6th column).

Marker-QC

=========

This file contains useful information about the SNPs and Indels in the data set. It is a plaintext file with space separated columns.

rs_id string rs_id (or affymetrix_snp_id if no rsid is available)

affymetrix_snp_id string id for marker from Affymetrix array definition

affymetrix_probeset_id string id for probeset from Affymetrix array definition

chromosome numeric Numeric chromosome label 1-26; 23=X,24=Y,25=XY,26=MT

position numeric Physical position of start of marker/Indel in GRCh37 coordinates

allele1_ref string Allele1 in the genotypes calls, aligned to ref allele

allele2_alt string Allele2 in the genotypes calls, aligned to alt allele

strand string Always '+' from Affymetrix array definition

array (0/1/2) Presence of marker on genotyping arrays 0=ukbl, 1=ukbb, 2=both

BATCH_qc (0/1) (no/yes) For each batch (Batch_b001-b095,UKBiLEVEAX_b1-b11), marker passed all QC tests

in_HetMiss (0/1) (no/yes) Marker was used in the calculation of heterozygosity and missingness

in_Relatedness (0/1) (no/yes) Marker was used in the calculation of kinship

in_PCA (0/1) (no/yes) Marker was used in the calculation of sample PCA

PC_loading numeric PCA snp_loadings for each of PC1-PC40

in_Phasing_Input (0/1) (no/yes) Marker was in the input for phasing

Sample-QC

=========

This file contains information about the samples in the data set.

The samples are in the same order as the calls FAM file. It is a plaintext file with space separated columns.

NOTE: there are currently 2 versions of this file in circulation. The newer

version is described below and contains column headers on the first row.

The older (deprecated) version lacks the column headers and has two

additional Affymetrix internal values prefixing the columns listed below.

genotyping.array string Indicates which array the DNA sample was typed on. UKBL=UK BiLEVE and UKBB=UK Biobank

Batch string Indicates in which batch Affymetrix called the genotypes for this sample. See Affymetrix documentation for details.

Plate.Name string Indicates on which plate Affymetrix processed this sample. See Affymetrix documentation for details.

Well string Indicates in which well Affymetrix processed sample. See Affymetrix documentation for details.

Cluster.CR numeric Affymetrix quality control metric. Corresponds to sample-specific call rate for each individual, computed using probesets internal to Affymetrix. See Affymetrix SNP-polisher documentation for details.

dQC numeric Affymetrix quality control metric. Measures the resolution of the distributions of intensity 'contrast' values, based on intensities of probe sequences for non-polymorphic genome locations. See Affymetrix SNP-polisher documentation for details. Note that values are rounded to 2 decimal places for individuals type on the UK Biobank array, and 5 decimal places for individuals typed on the UK BiLEVE array.

Internal.Pico..ng.uL. numeric Affymetrix quality control metric. Measure of DNA concentration in sample. See Affymetrix documentation for details.

Submitted.Gender string Gender submitted by participant. Should match UKBiobank phenotype field 'Sex'.

Inferred.Gender string Sex as determined by Affymetrix, and used in calling genotypes on the Y chromosome and the sex-specific region of the X chromosome. See Affymetrix documentation for details.

X.intensity numeric Affymetrix metric used for determining sex. Measures average probe intensity on a set of non-polymorphic probes on the X chromosome. Note this set of probes are not in the genotype calls.

Y.intensity numeric Affymetrix metric used for determining sex. Measures average probe intensity on a set of non-polymorphic probes on the Y chromosome. Note this set of probes are not in the genotype calls.

Submitted.Plate.Name string Indicates on which plate the DNA sample was delivered to Affymetrix. See UKBiobank DNA processing documentation for details.

Submitted.Well string Indicates in which well the DNA sample was delivered to Affymetrix. See UKBiobank DNA processing documentation for details.

sample.qc.missing.rate numeric Missing rate of each sample based on a set of high-quality markers. This metric was used to identify outliers based on heterozygosity and missing rates (het.missing.outliers). See genotype QC documentation for details.

heterozygosity numeric Heterozygosity across a set of high-quality markers. See genotype QC documentation for details.

heterozygosity.pc.corrected numeric Heterozygosity after adjusting for ancestry using principal components. This metric was used to identify outliers based on heterozygosity and missing rates (het.missing.outliers). See genotype QC documentation for details.

het.missing.outliers (0/1) (no/yes) Indicates samples identified as outliers in heterozygosity and missing rates, which indicates poor-quality genotypes for these samples.

putative.sex.chromosome.aneuploidy (0/1) (no/yes) Indicates samples identified as putatively carrying sex chromosome configurations that are not either XX or XY. These were identified by looking at average log2Ratios for Y and X chromosomes. See genotype QC documentation for details.

in.kinship.table (0/1) (no/yes) Indicates samples which have at least one relative among the set of genotyped individuals. These are exactly the set of samples that appear in the kinship table. See genotype QC documentation for details.

excluded.from.kinship.inference (0/1) (no/yes) Indicates samples which were excluded from the kinship inference procedure. See genotype QC documentation for details.

excess.relatives (0/1) (no/yes) Indicates samples which have more than 10 putative third-degree relatives in the kinship table.

in.white.British.ancestry.subset (0/1) (no/yes) Indicates samples who self-reported 'White British' and have very similar genetic ancestry based on a principal components analysis of the genotypes. See genotype QC documentation for details.

used.in.pca.calculation (0/1) (no/yes) Indicates samples which were used to compute principal components. All samples with genotype data were subsequently projected on to each of the 40 computed components. See genotype QC documentation for details.

PC1-PC40 numeric Score for each principal component 1-40. See genotype QC documentation for details.

in.Phasing.Input.chr1_22 (0/1) (no/yes) Indicates sample was in the input for phasing of chr1-chr22.

in.Phasing.Input.chrX (0/1) (no/yes) Indicates sample was in the input for phasing of chrX.

in.Phasing.Input.chrXY (0/1) (no/yes) Indicates sample was in the input for phasing of chrXY.

Relatedness

===========

This file lists the pairs of individuals related up to the third degree in the data set. It is a plaintext file with space separated columns.

ID1 string sample_id for individual 1 in related pair.

ID2 string sample_id for individual 2 in related pair.

HetHet numeric Fraction of markers for which the pair both have a heterozygous genotype (output from KING software).

IBS0 numeric Fraction of markers for which the pair shares zero alleles (output from KING software).

Kinship numeric Estimate of the kinship coefficient for this pair based on the set of markers used in the kinship inference (output from KING software). The set of markers is indicated by the field: used.in.kinship.inference

Imputation

==========

The imputed genotype calls are in BGEN v1.2 format (.bgen, .sample, .bgi) see http://www.well.ox.ac.uk/~gav/bgen_format/bgen_format_v1.2.html for details of the formats. The sample file lists the order of the samples in the .bgen files. The sample file includes the 'Sex' field for every sample (corresponding to 'Inferred.Gender' in the Sample-QC file). The list of variants in the files can be found with bgenix (https://bitbucket.org/gavinband/bgen/wiki/bgenix). The 1st column of the marker list file is 'alternate_ids' which is a unique identifier for each marker. For markers in the genotype data set 'alternate_ids' is the genotype marker id (rs_id in SNP-QC file). The second column is rsid or the reference panel marker_id, it is not guaranteed to be unique. The alleles in the imputation are aligned with REF/ALT, first_allele is the ref allele on the fwd strand.

Imputation MAF+info

===================

This file lists the minor allele frequency and info score for each of the markers in the imputed data, calculated using QCTOOL. The order of markers in these files is not guaranteed to be the same as the BGEN files.

Alternate_id

RS_id

Position

Allele1

Allele2

Minor Allele

MAF

Info score

Haplotypes

==========

The phased haplotypes are in BGEN v1.2 format (.bgen, .sample, .bgi) see http://www.well.ox.ac.uk/~gav/bgen_format/bgen_format_v1.2.html for details of the formats. The sample file lists the order of the samples in the .bgen files.

HLA imputation

==============

UK Biobank 500K HLA*IMP2 HLA Release

One file with all loci: A, B, C, DRB5, DRB4, DRB3, DRB1, DQB1, DQA1, DPB1, DPA1.

One line per individual.

The samples are in the same order as the calls FAM file.

Column 1:362 -> one column per possibly imputed allele. Includes all 11 HLA loci, and all possible alleles for each locus available from HLA*IMP:02.

The column headers are the allele names.The first part (before the "_") is the locus name e.g. A = HLA-A, DRB1 = HLA-DRB1 etc.The second part (after the "_") is the two field (formerly known as 4-digit) allele name for the locus. In this case if four digits are reported then the first two digits are the first field and the second two digits are the second field. The four digits give the 4-digit allele name in old HLA nomenclature. If three digits are reported, the first field is the first digit with a 0 to be added to the front, and the second field is the last two digits. In 4-digit notation one adds a 0 at the start.

For example

DRB1_403 = HLA-DRB1*04:03

whereas

DRB1_1101 = HLA-DRB1*11:01

For more information on HLA nomenclature see http://hla.alleles.org/nomenclature/naming.html

For HLA-DRB3, -DRB4, and -DRB5 the allele '9901' indicates that no allele is present (n.b. these loci can have copy number 0).

For each locus there are two imputations, giving the HLA genotype. Each has an associated probability. Non-imputed alleles are assigned probability 0 (only the maximum posterior probability alleles and their associated probabilities are reported). The imputed alleles are indicated by having a non-zero value in the relevant column for a given individual and locus: heterozygotes at a locus each have the maximum posterior probability from HLA*IMP:02 reported (Q2 in the HLA*IMP:02 output); homozygotes have the sum of these probabilities reported.

Intensity

=========

These files contains the A,B intensity data measured by Affymetrix. The files are in a simple custom binary format.

There are two intensity values A,B for each genotype, each represented as a 4-byte float. The set of A,B values for each marker are ordered consecutively by sample (analagous to a matrix with rows=SNPs and columns=Samples) e.g.

SNP_1_SAMPLE_1_A SNP_1_SAMPLE_1_B SNP_1_SAMPLE_2_A SNP_1_SAMPLE_2_B ... SNP_1_SAMPLE_N_A SNP_1_SAMPLE_N_B SNP_2_SAMPLE_1_A SNP_2_SAMPLE_1_B ...

Missing pairs of intensities are represented by -1 -1.

The order of the markers and Samples are given by the BIM and FAM files with the calls.

Affymetrix transform the A,B values into 'contrast' and 'strength' for their calling algorithm. If the intensity data is to be used for making cluster plots it is strongly suggested that the transformed values are plotted. The ellipses described by the snp-posterior data are only compatible with the transformed intensity values.

contrast (X) = log2(A/B)

strength (Y) = log2(AB)/2

Affymetrix called the genotypes in (106) batches of ~4,700 samples. To accurately examine the cluster plots, each batch should be plotted separately for a given marker. For chrX, males and females were called separately, so males and females should be plotted separately for chrX markers.

Evoker (https://github.com/wtsi-medical-genomics/evoker) can be used to plot cluster plots, following the recommendations above, for the UK Biobank data.

Confidences

===========

These files contain the Affymetrix 'confidence' that a genotype belongs to the call cluster. This is a plaintext file with space spearated columns.

Values are in the range 0-1 with 0 being most confident. Missing values are represented by -1. The order of markers and Samples are given by the BIM and FAM files.

CNV

===

These files contain the B-Allele-Frequency (baf) and Log2Ratio (log2r) transformed intensitiy values for performing CNV calling. There is a separate file for baf and log2r per chromosome. These are plaintext files with space separated columns. The rows corresond to markers (ordered as the calls BIM file) and the columns correspond to samples (ordered as the calls FAM file)

Missing values are represented by -1.

SNP-posterior

=============

These files contain parameters used in Affymetrix's genotype calling algorithm, such as the posterior probability distributions (2-dimensional multivariate Normal) for intensities (in 'contrast' and 'strength' coordinates) of each genotype at each marker. See the Applied Biosystems Axiom Genotyping Solution Data Analysis Guide for more details (http://tools.thermofisher.com/content/sfs/manuals/axiom_genotyping_solution_analysis_guide.pdf).

Affymetrix provide 33 parameters per marker per batch (3,498 per marker). Each parameter is represented by a 4-byte float. The set of values for each marker are ordered consecutively by batch. This is analagous to a matrix with rows=markers and columns=batch_parameters. The order of the markers and batches are given by the BIM and Batch files.

Diploid and haploid SNPs are called differently in Affymetrix' calling pipeline. On chrX females are diploid and males are haploid so we get two sets of parameters per SNP per batch. In the .bin snp-posterior chrX file, for each SNP the diploid and then the haploid snp-posteriors are given consecutively. The order of the SNPs is given in the BIM files, the haploid SNPs on chrX are appended with ':1' following Affymetrix' notation. The BIM files for chr1-22,Y,XY,MT are the same as for the calls files, but the chrX SNP-posterior BIM file has twice as many lines.

The 33 parameters are arranged in four groups. There are 7 parameters for each genotype cluster BB, AB, AA and a fourth set of 12 parameters (CV) from Affymetrix' pipeline which can be ignored for most analyses.

The 7 parameters per genotype cluster are five parameters which define a 2-dimensional multivariate Normal distribution, and two counts of observations (NObsMean,NObsVar) in the order:

mu_X

sigma_X

NObsMean

NObsVar

mu_Y

sigma_Y

cov

Missing values are represented using the IEEE 754 NaN.

File names

==========

Calls BED ukb_cal_chrN_v2.bed

Calls BIM ukb_snp_chrN_v2.bim

Calls FAM ukbA_cal_v2_sP.fam

Marker-QC ukb_snp_qc.txt

Sample-QC ukb_sqc_v2.txt

Relatedness ukbA_rel_sP.txt

Imputation BGEN ukb_imp_chrN_v3.bgen

Imputation BGI ukb_imp_chrN_v3.bgen.bgi

Imputation MAF+info ukb_mfi_chrN_v3.txt

Imputation sample chr1-22 ukbA_imp_chrN_v3_sP.sample

Imputation sample chrX ukbA_imp_chrX_v3_sP.sample

Imputation sample chrXY ukbA_imp_chrXY_v3_sP.sample

Haplotypes BGEN ukb_hap_chrN_v2.bgen

Haplotypes BGI ukb_hbg_chrN_v2.bgi

HLA Imputation ukb_hla_v2.txt

Intensity ukb_int_chrN_v2.bin

Confidences ukb_con_chrN_v2.txt

CNV log2r ukb_l2r_chrN_v2.txt

CNV baf ukb_baf_chrN_v2.txt

SNP-posterior ukb_snp_posterior_chrN.bin

Batch ukb_snp_posterior.batch

SNP-posterior chrX BIM ukb_snp_posterior_chrX_haploid.bim

N: chromosome label (1..22,X,Y,XY,MT)

P: number of consenting participants

A: researchers UK Biobank application ID