Linkage Analysis

Linkage analysis function is provided by the Merlin and MORGAN linkage function and FamPipe selects the regions with p-values less than Linkage_pvalue (the default value is 0.05).

Non-parametric linkage analysis

Command line options:
  • Calculate the Whittemore and Halpern NPL all using Merlin.
    --Linkage --npl
  • Calculate the Whittemore and Halpern NPL pairs using Merlin.
    --Linkage --pairs
  • Perform IBD-based tests using MORGAN
    --IBD_Morgan norm,Spairs

By default, FamPipe will perform the normality test based on the Spairs IBD measure in Morgan. Permutation test can be performed and other three IBD measures (Slambda, Srobdom, Saffect) provided in Morgan can be used. For example, to perform permutation test using Slambda, use “--IBD_Morgan permu,Slambda”

Related options:
  • Specify the threshold of linkage p-value (default value is 0.05)
    --Linkage_pvalue value
    Example:
    --Linkage_pvalue 0.1
  • Specify the grid for linkage analysis (Default is 1)
    --grid value
    Example:
    --grid 0.5
  • Memory saving option. Turning on this option will significant reduce the memory consumption in Merlin.
    --smallSwap
  • PLINK prune threshold (variance inflation factor, VIF). FamPipe uses PLINK to prune SNPs in LD using the VIF. SNPs that are not correlated are used for the linkage analysis. The default value of VIF is 2. Please see the PLINK manual “Linkage disequilibrium based SNP pruning” for more information.
    --vif value
    Example:
    --vif 1.5
  • MORGAN related options. These options can be specified if you use MORGAN:
    --MC value
    The default value is 100000
    --burn-in value
    The default value is 100
    --L-sampler value
    The default value is 0.2
    Please refer to the MORGAN user manual for more details about these options.
Output:
Two files (CHRX_linkage.txt and CHRX_range.txt) will be generated for each chromosome. CHRX_linkage.txt saves the Merlin linkage results and CHRX_range.txt saves the linkage regions (each row specifies the start and end physical positions) with p-values less than Linkage_pvalue.
Error/Warning:
  • -Warning: could not find the result in linkage Analysis.
    If you see this message, it means Merlin did not generate results.
  • -Warning: There is no pvalue smaller than Linkage_pvalue(threshold) in ‘CHR1_linkage.txt’. Interval file will not be generated.
    If you see this message, you won’t get “CHR1_range.txt” as there is no pvalue less than Linkage_pvalue threshold in Linkage output file (CHR1_linkage.txt).
For more information about the linkage analysis in Merlin, please see MERLIN Tutorial -- Linkage Analysis.
For more information about the IBD tests in MORGAN, please see the MORGAN Tutorial.

Parametric linkage analysis

Command line options:
  • Specify the disease penetrance functions P(aff|dd), P(aff|Dd), P(aff|DD), where D is the disease allele.
    --penetrance p1,p2,p3
    For example,
    --penetrance 0,0,1 would represent a recessive model with complete penetrance.
  • Calculate LOD scores using MORGAN
    --Linkage_Morgan
    This option will perform the "lm_linkage" function in MORGAN. To run "lm_bayes" in MORGAN, use "--Linkage_Morgan lm_bayes"
Related options:
  • Specify the threshold of linkage LOD score (default value is 0)
    --Linkage_LOD value
    For example,
    --Linkage_LOD 1