Search our Database of Scientific Publications and Authors

I’m looking for a

    Details and Download Full Text PDF:
    Genome-wide association and targeted analysis of copy number variants with psoriatic arthritis in German patients.

    BMC Med Genet 2017 08 23;18(1):92. Epub 2017 Aug 23.
    Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany.
    Background: Psoriatic Arthritis (PsA) is a chronic inflammatory disease of the joints. PsA is etiologically complex, and 11 susceptibility loci have been identified so far. Most of these overlap with loci associated with psoriasis vulgaris (PsV), the most common psoriatic skin manifestation which is also frequently seen in PsA patients. In addition, two copy number variants (CNVs) are associated with PsV, one of which, located within the LCE3 gene cluster, is also associated with PsA. Finally, an intergenic deletion has been reported as a PsA-specific CNV.

    Methods: We performed a genome-wide association study (GWAS) of CNVs in PsA and assessed the contribution to disease risk by CNVs at known psoriasis susceptibility loci.

    Results: After stringent quality assessment and validation of CNVs of the GWAS with an alternative quantitative method, two significantly associated CNVs remained, one near UXS1, the other one at the TRB locus. However, MLPA analysis did not confirm the CN state in ~1/3 of individuals, and an analysis of an independent case-control-study failed to confirm the initial associations. Furthermore, detailed PCR-based analysis of the sequence at TRB revealed the existence of a more complex genomic sequence most accurately represented by freeze hg18 which accordingly failed to confirm the hg19 sequence. Only rare CNVs were detected at psoriasis susceptibility loci. At three of 12 susceptibility loci with CNVs (CSMD1, IL12B, RYR2), CN variability was confirmed independently by MLPA. Overall, the rate of CNV confirmation by MLPA was strongly dependent upon CNV type, CNV size and the number of array markers involved in a CNV.

    Conclusion: Although we identified PsA associations at several loci and confirmed that the common CNVs at these sites were real, ~1/3 of the common CNV states could not be reproduced. Furthermore, replication analysis failed to confirm the original association. Furthermore, SNP array-based analyses of CNVs were found to be more reliable for deletions than duplications, independent of the respective CNV allele frequency. CNVs are thus good candidate disease variants, while the methods to detect them should be applied cautiously and reproduced by an independent method.
    PDF Download - Full Text Link
    ( Please be advised that this article is hosted on an external website not affiliated with
    Source Status ListingPossible

    Similar Publications

    A deletion at ADAMTS9-MAGI1 locus is associated with psoriatic arthritis risk.
    Ann Rheum Dis 2015 Oct 19;74(10):1875-81. Epub 2015 May 19.
    Rheumatology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain.
    Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach.

    Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Read More
    Genome-wide Association Analysis of Psoriatic Arthritis and Cutaneous Psoriasis Reveals Differences in Their Genetic Architecture.
    Am J Hum Genet 2015 Dec 28;97(6):816-36. Epub 2015 Nov 28.
    Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI 48105, USA. Electronic address:
    Psoriasis vulgaris (PsV) is a common inflammatory and hyperproliferative skin disease. Up to 30% of people with PsV eventually develop psoriatic arthritis (PsA), an inflammatory musculoskeletal condition. To discern differences in genetic risk factors for PsA and cutaneous-only psoriasis (PsC), we carried out a genome-wide association study (GWAS) of 1,430 PsA case subjects and 1,417 unaffected control subjects. Read More
    Investigation of 20 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris.
    Br J Dermatol 2013 May;168(5):1060-5
    Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Science, 27397 Jingshi Lu, Jinan Shandong, 250022, China.
    Background: Recently, a number of non-HLA (human leucocyte antigen) psoriasis genetic susceptibility loci have been identified through genome-wide association studies, but data on their association with psoriatic arthritis (PsA) are lacking.

    Objectives: To investigate recently identified psoriasis susceptibility loci in a cohort of Chinese patients with PsA, psoriasis vulgaris (PsV) and healthy controls.

    Methods: Twenty single-nucleotide polymorphisms (SNPs) from 20 loci were selected for genotyping in 379 patients with PsA, 595 patients with PsV and 1181 healthy controls using the MassARRAY platform (Sequenom, San Diego, CA, U. Read More
    Investigation of 36 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in a psoriatic arthritis cohort.
    Arch Dermatol Res 2017 Mar 17;309(2):71-77. Epub 2016 Dec 17.
    Department of Dermatology, Huashan Hospital, Fudan University, Wulumuqi Middle Road No 12, Shanghai, 200030, China.
    Psoriasis has been intensively studied recently and numerous risk-associated variants within 44 susceptibility loci have been discovered. Estimates suggest that the genetic contribution to PsA (psoriatic arthritis) may be higher than PsV (psoriasis vulgaris) yet most work has been done on the latter due to its greater population prevalence. To test whether variants in the PsV-associated loci are also related to PsA, we performed a candidate loci association study in Chinese population. Read More