title: Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis.
abstract: Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperproliferation and altered keratinocyte differentiation and inflammation and is caused by the interplay of genetic and environmental factors. Previous studies have revealed that DNA methylation (DNAm) and genetic makers are closely associated with psoriasis, and strong evidences have shown that DNAm can be controlled by genetic factors, which attracted us to evaluate the relationship among DNAm, genetic makers, and disease status.
  
  
  
  We utilized the genome-wide methylation data of psoriatic skin (PP,N= 114) and unaffected control skin (NN,N= 62) tissue samples in our previous study, and we performed whole-genome genotyping with peripheral blood of the same samples to evaluate the underlying genetic effect on skin DNA methylation. Causal inference test (CIT) was used to assess whether DNAm regulate genetic variation and gain a better understanding of the epigenetic basis of psoriasis susceptibility.
  
  
  
  We identified 129 SNP-CpG pairs achieving the significant association threshold, which constituted 28 unique methylation quantitative trait loci (MethQTL) and 34 unique CpGs. There are 18 SNPs were associated with psoriasis at a Bonferoni-correctedP< 0.05, and these 18 SNPs formed 93 SNP-CpG pairs with 17 unique CpG sites. We found that 11 of 93 SNP-CpG pairs, composed of 5 unique SNPs and 3 CpG sites, presented a methylation-mediated relationship between SNPs and psoriasis. The 3 CpG sites were located on the body ofC1orf106, the TSS1500 promoter region ofDMBX1and the body ofSIK3.
  
  
  
  This study revealed that DNAm of some genes can be controlled by genetic factors and also mediate risk variation for psoriasis in Chinese Han population and provided novel molecular insights into the pathogenesis of psoriasis.
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Fusheng
authors.identifier: 0000-0003-4195-2801
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA 02131 USA.|Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 USA.|Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
authors.forename: Changbing
authors.initials: C
authors.lastname: Shen
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Jingkai
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230601 Anhui China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Biochemistry, University of New Mexico, Albuquerque, NM 87131 NM USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Ko
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Jinfa
authors.initials: J
authors.lastname: Dou
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Xianfa
authors.initials: X
authors.lastname: Tang
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Genetics, and Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27517 USA.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029 China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109 USA.|Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109 USA.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: Lam C
authors.initials: LC
authors.lastname: Tsoi
authors.affiliation: Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA 02131 USA.|Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA 02115 USA.|Broad Institute of MIT and Harvard, Cambridge, MA 02142 USA.
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute and Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Meishan Road 81, Hefei, 230032 Anhui Province China.|The Key Laboratory of Dermatology, Ministry of Education, Anhui Medical University, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032 Anhui China.|Department of Dermatology, The Second Affiliated Hospital, Anhui Medical University, Hefei, 230601 Anhui China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002681:China / Q000208:ethnology; D019175:DNA Methylation; D057890:Epigenomics / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051857:Otx Transcription Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011565:Psoriasis / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: C465213:DMBX1 protein, human; D051857:Otx Transcription Factors; D011506:Proteins; D011494:Protein Kinases; C509079:SIK3 protein, human
keywords: DNA methylation; Epigenome; Genetic risk; Psoriasis