Epistasis Blog

From the Artificial Intelligence Innovation Lab at Cedars-Sinai Medical Center (www.epistasis.org)

Saturday, March 27, 2010

The discriminative accuracy of genomic profiling in the prediction of common complex diseases

I am enjoying the numerous papers appearing in the literature on the inability of genetic assoication results to accurately predict common complex diseases. The wake up call is here. My advice to current students is to forget everything you have learned over the last five years and go back and read the historical literature from geneticists that think deeply about genetic architecture. I started a reading list last year on Epistasis Blog. See the May 7, 2009 post on 100 papers every graduate student (in genetic epidemiology) should read.

Moonesinghe R, Liu T, Khoury MJ. Evaluation of the discriminative accuracy of genomic profiling in the prediction of common complex diseases. Eur J Hum Genet. 2010 Apr;18(4):485-9. [PubMed]


Genetic testing for susceptibility to common diseases based on a combination of genetic markers may be needed because the effect size associated with each genetic marker is small. Whether or not a genome profile based on a combination of markers could yield a useful test can be evaluated by assessing the discriminative accuracy. The authors present a simple method to calculate the clinical discriminative accuracy of a genomic profile when the relative risk and genotype frequency of each genotype are known. In addition, the clinical discriminative accuracy of a genetic test is presented for given values of the heritability and prevalence of the disease and for the population-attributable fraction of the combined genetic markers. For given values of relative risk and genotype frequency, the discriminative accuracy increases with increasing heritability but declines with increasing prevalence of the disease. For a given value of population-attributable fraction, the discriminative accuracy increases with increasing relative risks, but declines with increasing genotype frequency. On the basis of population-attributable fraction and estimates of heritability of disease, the number of risk genotypes required to have a reasonable clinical discriminative accuracy is much higher than the genome profiles available at present.


At 10:08 AM, Blogger G. F. Barbato said...

oh my goodness!! it was a real treat to read your commentary... i got a real chuckle. imho, we proscribe one too many biochem courses and a few too few genetics courses in our grad curricula.

having said that, showing my own peculiar biases, i would recommend that aspiring geneticists should revisit Dobzhansky's work. Interested in genetic architecture, you can't go wrong reading and rereading 'mather & jinks'.

then again, the trio of papers i revisit most often are george.clayton's papers from 1957. reading these, nothing should surprise you regarding the accuracy of 'genetic' predictions!


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