Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan

Abstract

In a 12.5 cM genome-wide scan for psoriasis susceptibility loci, recombination-based tests revealed linkage to the HLA region (Zmax = 3.52), as well as suggestive linkage to two novel regions: chromosome 16q (60-83.1 cM from pter, Zmax = 2.50), and chromosome 20p (7.5-25 cM from pter, Zmax = 2.62). All three regions yielded P values < or = 0.01 by non-parametric analysis. Recombination-based and allele sharing methods also confirmed a previous report of a dominant susceptibility locus on distal chromosome 17q (108.2 cM from pter, Zmax = 2.09, GENEHUNTER P = 0.0056). We could not confirm a previously reported locus on distal chromosome 4q; however, a broad region of unclear significance was identified proximal to this proposed locus (153.6-178.4 cM from pter, Zmax = 1.01). Taken together with our recent results demonstrating linkage to HLA-B and -C, this genome-wide scan identifies a psoriasis susceptibility locus at HLA, confirms linkage to 17q, and recommends two novel genomic regions for further scrutiny. One of these regions (16q) overlaps with a recently-identified susceptibility locus for Crohn's disease. Psoriasis is much more common in patients with Crohn's disease than in controls, suggesting that an immunomodulatory locus capable of influencing both diseases may reside in this region.

Genetic studies in familial ankylosing spondylitis susceptibility

“…The same results were seen again in GeneHunter Plus, with no new linkages found and previous linkages confirmed. Of note, the region seen on chromosome 16q was not overlapped with the region implicated in susceptibility to psoriasis (19).…”

“…Although we observed no psoriasis or IBD in patients with nonfamilial AS, there were no differences in other disease features (uveitis, heel pain) in the trio families, and there were no statistically significant differences between patients with familial versus nonfamilial AS. Moreover, these clinical features occur at similar frequencies in patients with sporadic AS (19). Nevertheless, because these families were referred to as multiplex families (in which familiality could not be confirmed), genetically we cannot rule out the possibility that they may not be truly representative of sporadic AS cases.…”

National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening

“…[131][132][133] Relatives of subjects diagnosed with either Crohn's or psoriasis also have been shown to have an increased incidence of having the other disease. 134 Genetic [135][136][137][138] and pathologic [139][140][141][142] connections between these two diseases support these findings, and most recently both have been linked to specific gentotypes of IL-23. 143 Two studies have shown that psoriasis is more common in MS families than in controls.…”

Meta‐Analysis of Linkage Studies for Complex Diseases: An Overview of Methods and a Simulation Study

“…GSMA needs at least one value of each study in each bin which is rarely the case if only interesting values are reported. However, more and more researchers distribute the detailed results of their analysis via the internet, such as NPL scores for each marker tested (as in a psoriasis scan by Nair et al 1997), where the multipoint statistics at regular intervals (as in a stature and BMI genome scan by Perola et al 2001) and the information content could be included. Besides, it is a long standing scientific tradition to retain data and intermediate results and to give other researchers the opportunity to verify the reported results by making materials and data available.…”