Common variants explain a large fraction of the variability in the liability to psoriasis in a Han Chinese population.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Xianyong
X
Yin
Nathan E
NE
Wineinger
Hui
H
Cheng
Yong
Y
Cui
Fusheng
F
Zhou
Xianbo
X
Zuo
Xiaodong
X
Zheng
Sen
S
Yang
Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province 230032, China. nschork@scripps.edu.
Nicholas J
NJ
Schork
Xuejun
X
Zhang
D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D002681:China; D005787:Gene Frequency; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D012372:ROC Curve
D006680:HLA Antigens