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Re: st: Gene-incidence question/simulation


From   Neil Shephard <nshephard@gmail.com>
To   statalist@hsphsun2.harvard.edu
Subject   Re: st: Gene-incidence question/simulation
Date   Mon, 23 Mar 2009 10:27:00 +0000

On Mon, Mar 23, 2009 at 10:15 AM, moleps islon <moleps2@gmail.com> wrote:
> Thanks for the statistical input. I truly appreciate this. However
> what I've done instead in order to get an estimate is to run a
> simulation whereby I select g random patients in my sample and "give
> them" the mutation and then do the usual calculations.

Sorry, but I see no benefit to this at all.  How are you estimating
the proportion of your sample to '"give them" the mutation'?

The frequency of the allele will be pivotal to calculating the
penetrance, and from your code all you've done is pick a random sample
of g patients from the total N.  This is highly unlikely to reflect
the true frequency of the polymorphism in the population, and all
you'll have is a range of estimates based on varying genotype
frequencies under a dominant model (see comment below).

Further your code doesn't seem to be explicitly accounting for any
form of genetic other than a dominant one and you may wish to consider
recessive, additive and multiplicative (after all, you presumably have
no idea about the mode of inheritance).

What organism are you looking at and what marker are you considering?
If its humans and a SNP, see if you can find the RS# on HapMap where
there will (hopefully) be an estimate of the allele frequency from
their standard populations.

I don't think you can draw any conclusions from the results that you
are obtaining here.  You really need to genotype your samples for the
mutation to estimate the allele frequency, determine the frequency of
each genotype in your data set and then you can start deriving the
penetrance and joint probability of developing the two phenotypes.

Regards

Neil
-- 
"The combination of some data and an aching desire for an answer does
not ensure that a reasonable answer can be extracted from a given body
of data." ~ John Tukey (1986), "Sunset salvo". The American
Statistician 40(1).

Email - nshephard@gmail.com
Website - http://slack.ser.man.ac.uk/
Photos - http://www.flickr.com/photos/slackline/
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