Navigation Links
The contribution of coding variants to psoriasis much smaller than thought
Date:11/10/2013

November 10, 2013, Shenzhen, China - 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 diseaserelated 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."


'/>"/>

Contact: Jia Liu
liujia@genomics.cn
BGI Shenzhen
Source:Eurekalert

Related biology news :

1. Nuclear weapons surprising contribution to climate science
2. Study provides first-time analysis of 3 distinct contributions of forage fish worldwide
3. Combining two genome analysis approaches supports immune system contribution to autism
4. UTSA anthropologist honored for contributions researching primates in Africa
5. Significant contribution of Greenlands peripheral glaciers to sea-level rise
6. Exploring the Latest Evidence of Dairys Contribution to Nutrition at IUNS Satellite Symposium
7. U of M research uncovers genes contribution to asthma susceptibility
8. Decoding worm lingo
9. DNA barcoding verified the discovery of a highly disconnected crane fly species
10. Decoding the secrets of balance
11. Study: DNA barcoding can ID natural health products
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/20/2017)... At this year,s CeBIT Chancellor Dr. Angela Merkel ... came to the DERMALOG stand together with the Japanese Prime Minster Shinzo ... At the largest German biometrics company the two government leaders could see ... as well as DERMALOG´s multi-biometrics system.   Continue ... ...
(Date:3/13/2017)... Future of security: Biometric Face Matching software  ... ... DERMALOGs Face Matching enables to match face pictures against each other or against ... (PRNewsFoto/Dermalog Identification Systems) ... Matching" is the fastest software for biometric Face Matching on the market. The ...
(Date:3/7/2017)... Brandwatch , the leading social intelligence company, today announces that ... uncover insights to support its reporting, help direct future campaigns, and ... youth charity will be using Brandwatch Analytics social listening and analytics ... of the topics and issues that are a priority for its ... "Until recently ...
Breaking Biology News(10 mins):
(Date:3/28/2017)... , ... March 28, 2017 , ... ... Phase II Small Business Innovation Research (SBIR) grant from the National Science Foundation ... over two years to develop a suite of BioGel™ biopolymer materials for hygiene ...
(Date:3/28/2017)... Summary This report provides all ... its partnering interests and activities since 2010. Description The ... insight into the partnering activity of one of the world,s ... are prepared upon purchase to ensure inclusion of the most ... report will be delivered in PDF format within 1 working ...
(Date:3/28/2017)... Belgium , March 28, 2017 ... (NYSE MKT: VNRX), today announced the engagement of Deborah ... LLC, as a strategic consultant. Dr. Vollmer Dahlke,s ... securing non-dilutive funding in the State of Texas ... . Dr. Vollmer Dahlke has significant experience ...
(Date:3/28/2017)... , March 28, 2017  Viking Therapeutics, Inc. ... the development of novel therapies for metabolic and endocrine ... Brian Lian , Ph.D., will deliver a corporate presentation ... NASH Investor Conference, being held April 3, 2017 at ... Details for this presentation are as follows: ...
Breaking Biology Technology: