Asian Scientist (Nov. 14, 2013) – Genetic variants that represent functional protein-coding changes may play only a small part in the overall genetic risk for psoriasis, according to a new study led by researchers in China.
The study, published in Nature Genetics, looked at the contribution of functional protein-coding genetic variants to psoriasis in 21,309 Chinese individuals. The researchers discovered only two independent low-frequency coding variants with moderate effect on disease risk from this large-scale investigation.
Psoriasis is a complex, chronic, lifelong skin disease. It typically first strikes people between the ages of 15 to 35, but can affect anyone at any age, including children. The disease may arise due to multiple factors, including the environment, genetics, and immunology.
Researchers had identified numerous risk-associated genetic variants in psoriasis, but functional coding variants, particularly low-frequency and rare variants, have not been systematically study.
In this study, researchers used a two-phase strategy to identify coding variants. In the discovery stage, they conducted exome sequencing on 781 patients with psoriasis and used 676 people without psoriasis as controls.
To confirm their findings in the discovery stage, the researchers performed 2 further independent studies in a large sample of 9,946 patients with psoriasis and 9,906 controls using targeted sequencing of the variants identified.
Through their analysis, the researchers identified only two low-frequency coding variants and 5 common coding variants that were associated with psoriasis. They also investigated 622 immune disease-related genes and showed that coding variants have limited independent contribution to psoriasis risk. Taken together, the study provides a strong indication coding variants in the 1,326 targeted genes had limited contribution to the overall genetic risk of psoriasis.
By comparing their results with previous work in a European population, the study also found genetic differences between European and Chinese people with psoriasis.
Xin Jin, co-author of this study at BGI, said, “Target sequencing in such a large sample size enables us to investigate full spectrum of variants in these region. Although we did not identify any low-frequency or rare coding variants with strong genetic effect, the data helps us to refine several known GWAS loci and identify some candidate casual variants. It remains to be shown whether limited contribution of rare coding variants will also hold true for other regions outside the target and in other common diseases beyond psoriasis.”
The article can be found at: Tang H et al. (2013) A Large-Scale Screen For Coding Variants Predisposing To Psoriasis.
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Source: BGI; Photo: mysiana/Flickr/CC.
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#Affiliated Hospital of Inner Mongolia Medical College #Anhui Medical University #BGI-Shenzhen #China #Chinese Academy of Medical Sciences #Chinese Academy of Sciences #Fudan University #Jining No. 1 People's Hospital #Navy General Hospital #No. 1 Hospital of China Medical University #Peking University #Peking University People's Hospital #Psoriasis #Second Affiliated Hospital of Harbin Medical University #Second Hospital Chengdu #Shandong Academy of Medical Science #South China University of Technology #Third People's Hospital of Hangzhou
