7-days of FREE Audio papers, translation & more with Prime
7-days of FREE Prime access
7-days of FREE Audio papers, translation & more with Prime
7-days of FREE Prime access
https://doi.org/10.1111/j.0022-202x.2004.23414.x
Copy DOIJournal: Journal of Investigative Dermatology | Publication Date: Sep 1, 2004 |
License type: publisher-specific-oa |
If the genetics of complex diseases is going to produce therapeutic advance, psoriasis is perhaps the best place to start. Psoriasis has one of the highest heritabilities of any common inflammatory disease and, just to make the decision easier, we have astonishingly little insight into key environmental determinants. Unlike, say, atopy, where marked secular changes have reportedly occurred, psoriasis epidemiology seems remarkably boring and uniform. Over the last several years, there has been an epidemic of allelic association studies published for many diseases, many in the Journal, and yet, armchair enthusiasts will notice that they have often been beset my methodological problems. All too often they have been less than statistically robust, and the magnitude of the effect size, smaller than the author's, and more importantly, the readers would wish for. Donn and colleagues in this issue report a positive association between macrophage migration inhibitory factor promoter polymorphisms and psoriasis. The magnitude of the odds ratio is, again, small (∼1.5–1.7), but in the authors' favor they have functional evidence that the promoter polymorphism studies are functionally significant, and that the amounts of their gene product are altered in psoriasis. Which way is the field going and how does this paper help? First, once we exclude human leucocyte antogen (HLA) effects, we have lost perhaps half of the heritability of psoriasis. Researchers are left trying to apportion this remaining variability between an ever-increasing range of loci. Second, and here is a paradox, we feel happier with associations we can predicate on a mechanistic model (in the case of this study, what was known about this cytokine), but what we want the genetics to do is to point us in the direction of pathways we did not know about. Otherwise, reverse genetics has become synonymous with biochemistry, losing some of its ability to offer magical insights along the way. Given that disease-state prediction is not critical, then this all means that either we have to get used to betting on weak evidence or cast around for some new insights.
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.