[R] Incomplete Trio in TDT analysis

Steve Buyske buyske at stat.rutgers.edu
Thu Apr 27 05:04:23 CEST 2006


Using only informative incomplete trios and dropping others turns out 
to bias the TDT (Curtis & Sham 95). There are a variety of 
modifications to handle case-parent trios, starting (I think) with 
Weinberg's 1999 paper that uses the EM algorithm and a 
likelihood-ratio test. I don't know of any of these methods that are 
implemented in R. Perhaps they are in the package that you are using 
but forgot to name.

Steve Buyske



At 8:26 PM -0400 4/26/06, Farrel Buchinsky wrote:
>I am involved in a study where, as in most of life, men demonstrate
>themselves to be recalcitrant. So while we have many probands and most of
>their mothers we only have about 50% of the trios being complete.
>
>I have been running tdt and trio.types. It appears as if it is ignoring the
>duos. Sometimes a duo can be informative. For instance
>Father ..missing
>Mother 1/2
>Proband 1/1
>This duo shows that for allele 2, this was clearly a case where 2 was
>untransmitted.
>Yet I do not think this family counts toward the output that is generated.
>Am I correct? How do I use R to do TDT analysis where duo's are used if they
>are informative?
>
>If you want further details...
>
>I made a subset that I called MessWith and it is made up of the first 24
>probands and their parents. 2 probands had neither a mother nor a father. Of
>the remaining, probands, 16 only had one parent.
>>  summary(Genotype.914186)
>
>Number of samples typed: 52 (72.2%)
>
>Allele Frequency: (2 alleles)
>    Count Proportion
>1     73        0.7
>2     31        0.3
>NA    40         NA
>
>
>Genotype Frequency:
>     Count Proportion
>1/1    26        0.5
>1/2    21        0.4
>2/2     5        0.1
>NA     20         NA
>
>Heterozygosity (Hu)  = 0.4225168
>Poly. Inf. Content   = 0.3309022
>
>tdt(Genotype.914186, MessWith, famid, pid, fatid, motid, sex, affected )
>         Transmission/disequilibrium test
>Data:   Genotype.914186
>
>Untransmitted allele frequencies, informative transmissions
>and exact P-values
>
>        Allele     Frequency   Transmitted Untransmitted       P-value
>             2        0.3333             3             2         1.000
>
>trio.types(Genotype.914186, MessWith, famid, pid, fatid, motid, sex,
>affected )
>
>Farrel Buchinsky, MD
>Pediatric Otolaryngologist
>Allegheny General Hospital
>Pittsburgh, PA
>
>
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