Featured Research

from universities, journals, and other organizations

Contribution of coding variants to psoriasis much smaller than thought

Date:
November 10, 2013
Source:
BGI Shenzhen
Summary:
Coding variants in immune disease-related genes play only a small part in the overall genetic risk for psoriasis, according to a new study.

Coding variants in immune disease-related genes play only a small part in the overall genetic risk for psoriasis, according to a new study led by Anhui Medical University and BGI. This conclusion is strongly supported by their investigation on the contribution of functional coding variants to psoriasis in 21,309 Chinese individuals. In such a large-scale investigation, researchers only discovered two independent low-frequency variants with moderate effect on disease risk. The latest study was published online in Nature Genetics.

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. This terrible disease is the results of the interaction of multiple factors, such as environment, genetics, and immunology. The rapid and cost-effective sequencing technologies have enabled researchers to dig out numerous risk-associated variants in psoriasis, but the functional coding variants, particularly low-frequency and rare variants, have not been systematically investigated.

In this study, researchers took two-phase to identify coding variants. In the discovery stage, they conducted exome sequencing on 781 patients with psoriasis and 676 people without psoriasis as control. The efforts yielded 518,308 single-nucleotide variants (SNVs). Of these variants, 20.62% were nonsynonymous, and 68.13% were rare.

Considering the limitation of sample size and techniques in the discovery stage, researchers performed 2 independent studies in a large sample of 9,946 patients with psoriasis and 9,906 controls using targeted sequencing. A total of 3.2 Mb of coding DNA surrounding the targeted regions of 1,326 genes (covering 133 SNVs, 622 immune disease-related genes, and some top genes) was captured. They totally identified 82,387 nonsynonymous SNVs, of which 97.07% were rare.

Through further analysis, they discovered two independent missense SNVs in IL23R and GJB2 with low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. The rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association with this disease.

In addition to the SNVs analysis, researchers investigated 622 immune disease-related genes, and the results showed that the coding variants, at least common and low-frequency nonsynonymous variants, have limited independent contribution to psoriasis risk. Taking all the findings together, the study indicated that nonsynonymous SNVs in the 1,326 targeted genes had limited contribution to the overall genetic risk of psoriasis.

Compared with previous work on European population, this research also demonstrated the genetic heterogeneity between European and Chinese populations. The missense variant (rs72474224) in GJB2 seemed to be specific to Chinese individuals, while the one (rs11209026) in IL23R was specific to European individuals. And another common missense variant (rs11652075) in CARD14 showed consistent between European and Chinese samples.

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."


Story Source:

The above story is based on materials provided by BGI Shenzhen. Note: Materials may be edited for content and length.


Journal Reference:

  1. Huayang Tang, Xin Jin, Yang Li, Hui Jiang, Xianfa Tang, Xu Yang, Hui Cheng, Ying Qiu, Gang Chen, Junpu Mei, Fusheng Zhou, Renhua Wu, Xianbo Zuo, Yong Zhang, Xiaodong Zheng, Qi Cai, Xianyong Yin, Cheng Quan, Haojing Shao, Yong Cui, Fangzhen Tian, Xia Zhao, Hong Liu, Fengli Xiao, Fengping Xu, Jianwen Han, Dongmei Shi, Anping Zhang, Cheng Zhou, Qibin Li, Xing Fan, Liya Lin, Hongqing Tian, Zaixing Wang, Huiling Fu, Fang Wang, Baoqi Yang, Shaowei Huang, Bo Liang, Xuefeng Xie, Yunqing Ren, Qingquan Gu, Guangdong Wen, Yulin Sun, Xueli Wu, Lin Dang, Min Xia, Junjun Shan, Tianhang Li, Lin Yang, Xiuyun Zhang, Yuzhen Li, Chundi He, Aie Xu, Liping Wei, Xiaohang Zhao, Xinghua Gao, Jinhua Xu, Furen Zhang, Jianzhong Zhang, Yingrui Li, Liangdan Sun, Jianjun Liu, Runsheng Chen, Sen Yang, Jun Wang, Xuejun Zhang. A large-scale screen for coding variants predisposing to psoriasis. Nature Genetics, 2013; DOI: 10.1038/ng.2827

Cite This Page:

BGI Shenzhen. "Contribution of coding variants to psoriasis much smaller than thought." ScienceDaily. ScienceDaily, 10 November 2013. <www.sciencedaily.com/releases/2013/11/131110184406.htm>.
BGI Shenzhen. (2013, November 10). Contribution of coding variants to psoriasis much smaller than thought. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2013/11/131110184406.htm
BGI Shenzhen. "Contribution of coding variants to psoriasis much smaller than thought." ScienceDaily. www.sciencedaily.com/releases/2013/11/131110184406.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins