The many problems of GWAs

genetic-future has an excellent article why the recent genome scans failed (i) alleles with small effects? (ii) population differences? (iii) epistatic interactions? (iv) cnvs more relevant than snps? (v) epigenetic inheritance? (vi) disease heterogeneity? It is a thorough review better than everything that I have seen so far in the published literature.
A new (not FBI sponsored) GWA on hair color and skin pigmentation writes that

with new technologies that enable genotyping of hundreds of thousands of single nucleotide polymorphisms (SNPs), together with new insights into the structure of variation in the human genome […], it is now possible to scan the genome in an agnostic manner in search of common genetic variants […]

I believe they wanted to say “unbiased” – or even “ignorant”? BTW “Agnostic” is

a philosophical view that the truth value of certain claims — particularly metaphysical claims regarding theology, afterlife or the existence of God, gods, deities, or even ultimate reality — is unknown or, depending on the form of agnosticism, inherently unknowable.

and certainly reflects more my current view of complex disease genetics.


  1. Hi Matthias,
    You might like this commentary by Pat Sullivan. It provides a nice metaphor about levels of evidence – this is useful as we travel the ‘dark’ days of unravelling the hidden complexity of phenotypes like schizophrenia, asthma/allergies etc.


    Psychol Med. 2008 Jun 4:1-4. [Epub ahead of print]

    The dice are rolling for schizophrenia genetics.

    Sullivan PF.

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