期刊
BMC GENOMICS
卷 15, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2164-15-87
关键词
Psoriasis; Polygenic; Genome-wide association study; Heritability
资金
- Normal Project [81370044]
- Youth Project [81000692]
- key Project of National Natural Science Foundation of China [81130031]
- China Council of Scholarship [201208340003]
- NIH [5 UL1 RR025774, R21 AI085374, 5 U01 DA024417, \5 R01 HL089655, 5 R01 DA030976, 5 R01 AG035020, 1 R01 MH093500, 2 U19 AI063603, 2 U19 AG023122, 5 P01 AG027734, 1 R21 DA033813]
- Johnson and Johnson
- Veteran's Administration
- Viterbi Foundation
- Stand-Up-to-Cancer organization
- Price Foundation
- Scripps Genomic Medicine
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 x 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 (R-2 = 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.
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