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LAMP -- Program Options
Input Files and Basic Parameters
-d datafile - Selects input data file, in MERLIN format.
-p pedfile - Selects pedigree file, with genotype, phenotype and family structure information.
-f framework map file - Selects map file for flanking markers. See section on Input Format for further
details. This file is optional.
-c candidate map file - Selects map file for candidate SNPs and locations. See section on
Input Format for further details.
Additional options
Genetic Model Constraints
LAMP can optimize an unconstrained genetic model or can be direct to
use an additive, dominant, recessive or multiplicative model. When
accurately specified, constrained models reduce the number of parameters
to be estimated and can increase power. In addition, you should always
set the prevalence to a value appropriate for your disease.
--additive - Assumes that the heterozygote genotype has an intermediate
penetrance in relation to the two homozygotes.
--recessive - Assumes that an effect on penetrance is only seen for homozygous
genotypes.
--dominance - Assumes that an identical effect on penetrance is seen for individuals
who carry one or two copies of the risk allele.
--multiplicative - Assumes that the penetrance is multiplied by a constant factor
with each additional copy of the risk allele.
--free - This gives an unconstrained genetic model.
--prevalence - This option fixes the prevalence at the user-specified value. The
default prevalence is set at 0.05.
Note that the dominant and recessive models lead to identical likelihoods
since, for a two-allele disease model, finding one dominant allele implies that
a recessive allele is also present!
Parameter Constraints
Depending on your sampling strategy, not all parameters may be identifiable.
LAMP uses some simple rules to decide what parameters can be estimated in
each sample, but it is sometimes wrong. You can override LAMP's automatic
choice with one of the options.
--ignore-linkage
This option specifies that all linkage information should be ignored.
When the option is selected, LAMP will only fit models that imply direct
association between each evaluated marker and the trait. The option is
always appropriate for samples of unrelated individuals and for trio
data, but can also be useful in other samples that include very little
information about genetic linkage. We commonly use it for the
analysis of genome-wide association scans. The option was formerly
known as --unrelateds-and-trios.
--sibpairs
Ascertained sibling pair samples that include only affected sibpairs, only
unaffected sibpairs, or only discordant sibpairs contain limited information
on genetic linkage. When dealing with these samples and no genetic
model is specified, LAMP fixes the
allele frequency for linkage models to be the square root of the penetrance.
This results in no loss of power, but makes the model identifiable.
--none
Do not place any constraints on the allele frequencies and penetrance parameters
--auto
Apply some simple rules to try and automatically classify the available sample.
Optimization Strategy
When fitting a genetic model, LAMP maximizes a likelihood numerically. There
are a number of alternative optimization strategies to choose from and it is
also possible to restart each of the strategies from different randomly selected
parameter settings.
--fletcher-reeves - This is a quasi-Newton method that uses partial derivatives
calculated numerically.
--nelder-mead - This is the default optimizer based on the simplex method. It is
quite robust and seems to perform well in most settings.
--stochastic - This optimizer implements a stochastic search procedure, as
described by Storn and Price (1996). It appears to perform well,
but is quite slow.
--rounds n - At each stage, select n different starting points and
repeat the optimization procedure. This is a good final check
for the most exciting findings.
--precision x - Numeric optimization will stop when the relative improvement
in the log-likelihood is smaller than x. By default, x is set
to 10-8.
Performance
These options help tune the performance of LAMP and can be used
to tweak memory and computing time requirements.
--maxbits n - The maximum complexity of pedigrees that LAMP will try to analyze.
Lowering this value will result in discarding of large pedigrees,
while increasing it will result in attempts to analyze more complex
pedigrees and longer run-times. Bit complexity refers to the depth
of the
gene-flow trees used to represent the pedigree internally.
--buffers - By default, LAMP buffers intermediate results to try and speed up
calculations. This increases memory use and may not be very helpful
in datasets that include only a few large pedigrees. To disable
buffering, add the --buffers:OFF option to the command line.
--skipCausality - The causality test is most useful after identifying one more
associated SNPs. This option can be used to disable the test
in first pass analyses, therefore saving time.
Output Files
There are two options to control generation of output files:
--nodetails - This option can be used to suppress generation of detailed output
files and therefore preserve diskspace. When this option is not used,
LAMP generates a series of files to summarize estimated model parameters.
(By default, these are called lamp-base.out, lamp-linkage.out,
lamp-direct-association.out and lamp-indirect-association.out.)
--prefix string - This option can be used to control the name of detailed output
files. It is convenient when LAMP is run multiple times in the same
directory.
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