D: 18 Apr 2024

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LD-based result clumping

--clump ['zs'] ['cols='<col set desc.>] <PLINK report filename(s)...>

--clump-p1 <index variant p-value threshold>
--clump-p2 <SP2 column p-value threshold>
--clump-r2 <r^2 threshold>
--clump-kb <clump kb radius>

--clump-unphased
--clump-log10 ['input-only' | 'output-only']
--clump-log10-p1 <-log10(index variant p-value threshold)>
--clump-log10-p2 <-log10(SP2 column p-value threshold)>
--clump-bins <p-value bin boundaries...>

--clump-id-field <field name(s)...>
  (alias: --clump-snp-field)
--clump-p-field <field name(s)...>
  (alias: --clump-field)

--clump-a1-field [field name(s)...]
--clump-test-field [field name(s)...]
--clump-force-a1
--clump-test <test name(s)...>

--clump-allow-overlap

When there are multiple significant association p-values in the same region, LD should be taken into account when interpreting the results. The --clump command is designed to help with this.

--clump loads the named PLINK-format association report(s) (text files with a header line, a column containing variant IDs, and another column containing p-values) and groups results into LD-based clumps, writing a new report to plink2.clumps[.zst]. Multiple filenames can be separated by spaces or commas.

• Clumps are formed around central "index variants" which, by default, must have p-value no larger than 0.0001; change this threshold with --clump-p1. Index variants are chosen greedily starting with the lowest p-value. Variants which meet the --clump-p1 threshold, but have already been assigned to another clump, do not start their own clumps.
• Sites which are less than 250 kb away from an index variant and have r² larger than 0.5 with it are assigned to that index variant's clump (unless they have been previously been assigned to another clump, and --clump-allow-overlap is not in effect). These two thresholds can be changed with --clump-kb and --clump-r2, respectively.
• By default, the r² values computed by --clump are haplotype-based; maximum likelihood haplotype frequency estimates are applied to unphased data. Use --clump-unphased to change this to unphased r²; the resulting correlation coefficients are less accurate measures of LD, but they are more accurate measures of --glm genotype-column similarity (since --glm also doesn't use phase information).
• When dosages are present, they are now used in the r² computation.
• As usual, only founders are considered in the r² computation. If your dataset has a shortage of them, --make-founders may come in handy.
• By default, a p-value histogram is given for each clump, with default bin boundaries 0.0001,0.001,0.01,0.05. You can control the bin boundaries with --clump-bins; provide a comma- or space-separated sequence of increasing numbers.
• Sites within the clump which have association p-value smaller than 0.01 are listed in the 'SP2' column of the main report. This threshold can be adjusted with --clump-p2.
• By default, variant IDs are expected to be in the 'ID' column, or if that's absent, 'SNP'. You can change this with the --clump-id-field flag, which takes a space-delimited sequence of field names to search for. With multiple field names, earlier names take precedence over later ones. (The other --clump-...-field flags work the same way.)
• --clump-log10 specifies -log10(p) rather than raw p-value input/output. The 'input-only' and 'output-only' modifiers let you convert from one format to the other.
• By default, p-values are expected to be in the 'P' column (or, with --clump-log10, 'LOG10_P' and 'NEG_LOG10_P' are also recognized); change this with --clump-p-field.
• Multiallelic variants are effectively split in this computation. This requires the input file(s) to contain an effect-allele column; by default, this is expected to be 'A1', but you can change this with --clump-a1-field. A1 alleles aren't normally checked or reported for biallelic variants (since they usually don't affect p-values), but you can change that with --clump-force-a1.
• Entries in the SP2 column are now of the form <variant ID>[(A1 allele)][(file number)]. The A1 component normally only appears for multiallelic variants; --clump-force-a1 changes this. The file-number component now only defaults to appearing when more than one input file is provided; this can be changed with "cols=+f".
• By default, if there is a 'TEST' column, only lines where the test value is 'ADD' are considered. (This is a change from PLINK 1.x.) These default values can be changed with --clump-test-field and --clump-test, respectively.
• By default, no variant may belong to more than one clump; remove this restriction with --clump-allow-overlap.
• When variant IDs with p ≤ --clump-p1 threshold are present in a --clump input file, but missing from the main dataset, they are now written to plink2.clumps.missing_id[.zst]. When (variant ID, A1 allele) pairs with with p ≤ --clump-p1 threshold in the --clump input file are ignored due to the A1 allele being missing from the main dataset (note that A1 is only checked for multiallelic variants and --clump-force-a1), they are written to plink2.clumps.missing_allele[.zst].
• We have provisionally retired --clump's other bells and whistles; contact us if this is a problem.

The PLINK 1.07 documentation has more discussion of these flags, including a few detailed examples.

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