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Stahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, Voight BF, Kraft P, Chen R, Kallberg HJ, Kurreeman FA, , , Kathiresan S, Wijmenga C, Gregersen PK, Alfredsson L, Siminovitch KA, Worthington J, de Bakker PI, Raychaudhuri S, Plenge RM. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat Genet . 2012 Mar 25 ; PubMed Abstract

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Comment by:  Patrick Sullivan, SRF Advisor
Submitted 3 April 2012 Posted 3 April 2012

This paper is not about schizophrenia, but holds lessons for those interested in the oft-debated genetic architecture of complex traits.

There are now substantial data that schizophrenia is highly polygenic (Purcell et al., 2009 and Ripke et al., 2011)—hundreds and perhaps thousands of different genetic variants at different places in the genome each contribute a small portion of risk. Indeed, such loci account for a substantial portion of the variance in liability to schizophrenia, on the order of 25-33 percent (Ripke et al., 2011 and Lee et al., 2012), a substantial fraction of the heritability of schizophrenia (65-81 percent; Sullivan et al., 2003 and Lichtenstein et al., 2009).

Two large studies have shown that human height and body mass are also highly polygenic. Other studies have...  Read more

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