TY - JOUR
T1 - Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus
AU - Kunz, Manfred
AU - Konig, Inke R.
AU - Schillert, Arne
AU - Kruppa, Jochen
AU - Ziegler, Andreas
AU - Grallert, Harald
AU - Muller-Nurasyid, Martina
AU - Lieb, Wolfgang
AU - Franke, Andre
AU - Ranki, Annamari
AU - Panelius, Jaana
AU - Koskenmies, Sari
AU - Hasan, Taina
AU - Kere, Juha
AU - Ronn, Ann Charlotte
AU - Simon, Jan C.
AU - Schmidt, Enno
AU - Wenzel, Joerg
AU - Tuting, Thomas
AU - Landsberg, Jennifer
AU - Zeller, Tanja
AU - Blankenberg, Stefan
AU - Glaser, Regine
AU - Patsinakidis, Nikolaos
AU - Kuhn, Annegret
AU - Ibrahim, Saleh M.
N1 - Publisher Copyright:
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms (SNPs) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNPs in 219 case subjects and 262 controls from Finland. Association was particularly pronounced at 4 loci, all with genomewide significance (P < 5 × 10-8): rs2187668 (PGWAS = 1.4 × 10-12), rs9267531 (PGWAS = 4.7 × 10-10), rs4410767 (PGWAS = 1.0 × 10-9) and rs3094084 (PGWAS = 1.1 × 10-9). All mentioned SNPs are located within the major histocompatibility complex (MHC) region of chromosome 6 and near genes of known immune functions or associations with other autoimmune diseases such as HLA-DQ alpha chain 1 (HLA-DQA1), MICA, MICB, MSH5, TRIM39 and RPP21. For example, TRIM39/RPP21 read through transcript is a known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genomewide analysis of disease association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLA-DQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39 and RPP21).
AB - Cutaneous lupus erythematosus (CLE) is a chronic autoimmune disease of the skin with typical clinical manifestations. Here, we genotyped 906 600 single nucleotide polymorphisms (SNPs) in 183 CLE cases and 1288 controls of Central European ancestry. Replication was performed for 13 SNPs in 219 case subjects and 262 controls from Finland. Association was particularly pronounced at 4 loci, all with genomewide significance (P < 5 × 10-8): rs2187668 (PGWAS = 1.4 × 10-12), rs9267531 (PGWAS = 4.7 × 10-10), rs4410767 (PGWAS = 1.0 × 10-9) and rs3094084 (PGWAS = 1.1 × 10-9). All mentioned SNPs are located within the major histocompatibility complex (MHC) region of chromosome 6 and near genes of known immune functions or associations with other autoimmune diseases such as HLA-DQ alpha chain 1 (HLA-DQA1), MICA, MICB, MSH5, TRIM39 and RPP21. For example, TRIM39/RPP21 read through transcript is a known mediator of the interferon response, a central pathway involved in the pathogenesis of CLE and systemic lupus erythematosus (SLE). Taken together, this genomewide analysis of disease association of CLE identified candidate genes and genomic regions that may contribute to pathogenic mechanisms in CLE via dysregulated antigen presentation (HLA-DQA1), apoptosis regulation, RNA processing and interferon response (MICA, MICB, MSH5, TRIM39 and RPP21).
KW - Autoimmune diseases
KW - Genetics
KW - Lupus
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=84931572782&partnerID=8YFLogxK
U2 - 10.1111/exd.12708
DO - 10.1111/exd.12708
M3 - Article
C2 - 25827949
AN - SCOPUS:84931572782
SN - 0906-6705
VL - 24
SP - 510
EP - 515
JO - Experimental Dermatology
JF - Experimental Dermatology
IS - 7
ER -