NEW YORK (GenomeWeb) – An international team has tracked down new psoriasis risk variants that it detected through a meta-analysis of genome-wide association data for tens of thousands of individuals with Caucasian or Chinese ancestry.
As they reported in Nature Communications, the researchers initially examined data sets from five published and two unpublished GWAS, representing nearly 8,600 individuals with psoriasis and more than 13,900 unaffected controls. The search led to four new psoriasis-associated loci falling in enhancer regions for genes involved in the regulation of epidermal keratinocyte cells — results the researchers validated in another 21,000 or so cases and controls from seven study cohorts.
But the team also uncovered a handful of secondary associations, along with variants at loci within immune-related regions and beyond that showed ties to psoriasis in just one of the populations.
"Together, these results provide novel biological insights into the involvement of immune and keratinocyte development," the study's authors wrote, "but also demonstrate a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations."
Psoriasis affects a lower proportion of Asian individuals than individuals with European ancestry, the team noted. Whereas some 2.5 percent of Europeans are afflicted with the chronic, inflammatory skin condition, it turns up in only between 0.1 percent and half a percent of Asians.
There can be also differences in psoriasis symptoms, severity, and treatment response, the study's authors explained, spurring interest in a more complete understanding of the genes and pathways that can go awry in the condition.
To build from the dozens of variants implicated in psoriasis from past GWAS, the team started with a "trans-ethnic" meta-analysis of data from seven GWAS that tested 3,496 individuals of European ancestry and 5,186 unaffected controls from the same population, along with 5,084 Chinese cases and 8,732 Chinese controls.
When they compared directly genotyped and imputed variant patterns in the Chinese, Caucasian, or combined case-control groups, the researchers saw 43 suspicious SNPs that had not been linked to psoriasis previously.
After genotyping these SNPs in 10,285 cases and 10,785 controls from five European and two Chinese replication cohorts, the team was left with four significant associations in the European population and in the combined analysis: sites in and around the COG6, RUNX1, TP63, and LOC144817 genes.
The variants, which fell in enhancer sites that operate in keratinocyte cells, showed more tenuous ties to psoriasis in the Chinese population, where SNPs neighboring LOC144817 and COG6 reached nominal significance.
In addition to variants near RUNX1 and TP63, the researchers narrowed in on nine other loci that appear to be linked to psoriasis in those of European descent but not in Asian individuals.
Their follow-up experiments also identified variants in linkage disequilibrium with new or previously described psoriasis risk variants and refined associations within the MHC.