Genotypic variability based genome-wide association study identifies non additive loci HLA-C and IL12B for psoriasis

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Abstract

Genome-wide association studies (GWASs) have identified a number of loci for psoriasis but largely ignored non-additive effects. We report a genotypic variability based GWAS (vGWAS) that can prioritize non-additive loci without requiring prior knowledge of interaction types or interacting factors in two steps, using a mixed model to partition dichotomous phenotypes into an additive component and non additive environmental residuals on the liability scale and then the Levene’s (Brown-Forsythe) test to assess equality of the residual variances across genotype groups genome-widely. The vGWAS identified two genome-wide significant (P < 5.0e-08) non-additive loci HLA-C and IL12B that were also genome-wide significant in an accompanying GWAS in the discovery cohort. Both loci were statistically replicated in vGWAS of an independent cohort with a small sample size. HLA-C and IL12B were reported in moderate gene-gene and/or gene-environment interactions in several occasions. We found a moderate interaction with age-of-onset of psoriasis which was replicated indirectly. The vGWAS also revealed five suggestive loci (P < 6.76e-05) including FUT2 that was associated with psoriasis with environmental aspects triggered by virus infection and/or metabolic factors. Replication and functional investigation are needed to validate the suggestive vGWAS loci.
Original languageEnglish
Pages (from-to)289–296
JournalJournal of Human Genetics
Volume63
Issue number3
Early online date19 Dec 2017
DOIs
Publication statusPublished - 2018

Keywords

  • Journal Article

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