PMID- 29771307
OWN - NLM
STAT- MEDLINE
DCOM- 20191203
LR  - 20231104
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 27
IP  - 15
DP  - 2018 Aug 1
TI  - Assessment of rosacea symptom severity by genome-wide association study and 
      expression analysis highlights immuno-inflammatory and skin pigmentation genes.
PG  - 2762-2772
LID - 10.1093/hmg/ddy184 [doi]
AB  - Rosacea is a common, chronic skin disease of variable severity with limited 
      treatment options. The cause of rosacea is unknown, but it is believed to be due 
      to a combination of hereditary and environmental factors. Little is known about 
      the genetics of the disease. We performed a genome-wide association study (GWAS) 
      of rosacea symptom severity with data from 73 265 research participants of 
      European ancestry from the 23andMe customer base. Seven loci had variants 
      associated with rosacea at the genome-wide significance level (P < 5 x 10-8). 
      Further analyses highlighted likely gene regions or effector genes including IRF4 
      (P = 1.5 x 10-17), a human leukocyte antigen (HLA) region flanked by PSMB9 and 
      HLA-DMB (P = 2.2 x 10-15), HERC2-OCA2 (P = 4.2 x 10-12), SLC45A2 
      (P = 1.7 x 10-10), IL13 (P = 2.8 x 10-9), a region flanked by NRXN3 and DIO2 
      (P = 4.1 x 10-9), and a region flanked by OVOL1and SNX32 (P = 1.2 x 10-8). All 
      associations with rosacea were novel except for the HLA locus. Two of these loci 
      (HERC-OCA2 and SLC45A2) and another precedented variant (rs1805007 in 
      melanocortin 1 receptor) with an association P value just below the significance 
      threshold (P = 1.3 x 10-7) have been previously associated with skin phenotypes 
      and pigmentation, two of these loci are linked to immuno-inflammation phenotypes 
      (IL13 and PSMB9-HLA-DMA) and one has been associated with both categories (IRF4). 
      Genes within three loci (PSMB9-HLA-DMA, HERC-OCA2 and NRX3-DIO2) were 
      differentially expressed in a previously published clinical rosacea 
      transcriptomics study that compared lesional to non-lesional samples. The 
      identified loci provide specificity of inflammatory mechanisms in rosacea, and 
      identify potential pathways for therapeutic intervention.
CI  - (c) The Author(s) 2018. Published by Oxford University Press. All rights reserved. 
      For permissions, please email: journals.permissions@oup.com.
FAU - Aponte, Jennifer L
AU  - Aponte JL
AD  - Genomic Medicine, PAREXEL International, Research Triangle Park, NC, USA.
FAU - Chiano, Mathias N
AU  - Chiano MN
AD  - Target Sciences, GlaxoSmithKline, Stevenage, UK.
FAU - Yerges-Armstrong, Laura M
AU  - Yerges-Armstrong LM
AD  - Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
FAU - Hinds, David A
AU  - Hinds DA
AD  - 23andMe Inc., Mountain View, CA, USA.
FAU - Tian, Chao
AU  - Tian C
AD  - 23andMe Inc., Mountain View, CA, USA.
FAU - Gupta, Akanksha
AU  - Gupta A
AD  - Translational Science, Dermatology, GlaxoSmithKline, Research Triangle Park, NC, 
      USA.
FAU - Guo, Cong
AU  - Guo C
AD  - Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
FAU - Fraser, Dana J
AU  - Fraser DJ
AD  - Genomic Medicine, PAREXEL International, Research Triangle Park, NC, USA.
FAU - Freudenberg, Johannes M
AU  - Freudenberg JM
AD  - Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
FAU - Rajpal, Deepak K
AU  - Rajpal DK
AD  - Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
FAU - Ehm, Margaret G
AU  - Ehm MG
AD  - Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
FAU - Waterworth, Dawn M
AU  - Waterworth DM
AD  - Target Sciences, GlaxoSmithKline, Collegeville, PA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DM antigens)
RN  - 0 (IL13 protein, human)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Interleukin-13)
RN  - 0 (SNX33 protein, human)
RN  - 0 (Sorting Nexins)
RN  - 0 (interferon regulatory factor-4)
RN  - 144416-78-4 (LMP-2 protein)
RN  - EC 2.3.2.27 (HERC2 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Adult
MH  - Cysteine Endopeptidases/genetics
MH  - Female
MH  - Gene Expression Regulation
MH  - Genome-Wide Association Study
MH  - Guanine Nucleotide Exchange Factors/genetics
MH  - HLA-D Antigens/genetics
MH  - Humans
MH  - Interferon Regulatory Factors/genetics
MH  - Interleukin-13/genetics
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Rosacea/*etiology/genetics
MH  - Skin Pigmentation/*genetics
MH  - Sorting Nexins/genetics
MH  - Ubiquitin-Protein Ligases
PMC - PMC6822543
EDAT- 2018/05/18 06:00
MHDA- 2019/12/04 06:00
PMCR- 2018/05/16
CRDT- 2018/05/18 06:00
PHST- 2017/11/03 00:00 [received]
PHST- 2018/05/07 00:00 [revised]
PHST- 2018/05/09 00:00 [accepted]
PHST- 2018/05/18 06:00 [pubmed]
PHST- 2019/12/04 06:00 [medline]
PHST- 2018/05/18 06:00 [entrez]
PHST- 2018/05/16 00:00 [pmc-release]
AID - 4996740 [pii]
AID - ddy184 [pii]
AID - 10.1093/hmg/ddy184 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2018 Aug 1;27(15):2762-2772. doi: 10.1093/hmg/ddy184.