Common variants explain a large fraction of the variability in the liability to psoriasis in a Han Chinese population
1 Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province 230032, China
2 Key lab of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province 230032, China
3 Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province 230032, China
4 Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province 230032, China
5 Scripps Health, La Jolla, CA 92037, USA
6 The Scripps Translational Science Institute, La Jolla, CA 92037, USA
7 Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
BMC Genomics 2014, 15:87 doi:10.1186/1471-2164-15-87Published: 30 January 2014
Psoriasis is a common inflammatory skin disease with a known genetic component. Our previously published psoriasis genome-wide association study identified dozens of novel susceptibility loci in Han Chinese. However, these markers explained only a small fraction of the estimated heritable component of psoriasis. To better understand the unknown yet likely polygenic architecture in psoriasis, we applied a linear mixed model to quantify the variation in the liability to psoriasis explained by common genetic markers (minor allele frequency > 0.01) in a Han Chinese population.
We explored the polygenic genetic architecture of psoriasis using genome-wide association data from 2,271 Han Chinese individuals. We estimated that 34.9% (s.e. = 6.0%, P = 9 × 10-9) of the variation in the liability to psoriasis is captured by common genotyped and imputed variants. We discuss these results in the context of the strong association between HLA variants and psoriasis. We also show that the variance explained by each chromosome is linearly correlated to its length (R2 = 0.27, P=0.01), and quantify the impact of a polygenic effect on the prediction and diagnosis of psoriasis.
Our results suggest that psoriasis has a substantial polygenic component, which not only has implications for the development of genetic diagnostics and prognostics for psoriasis, but also suggests that more individual variants contributing to psoriasis may be detected if sample sizes in future association studies are increased.