单位：[1]Institute and Department of Dermatology, The First Affiliated Hospital,Anhui Medical University, Meishan Road 81, Hefei 230032, Anhui Province,China[2]The Key Laboratory of Dermatology, Ministry of Education, AnhuiMedical University, Anhui, China[3]Collaborative Innovation Center forComplex and Severe Dermatosis, Anhui Medical University, Hefei 230032,Anhui, China[4]Hebrew SeniorLife Institute for Aging Research and HarvardMedical School, Boston, MA 02131, USA[5]Molecular and IntegrativePhysiological Sciences, Harvard School of Public Health, Boston, MA 02115,USA[6]Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA[7]Department of Dermatology, The Second Affiliated Hospital, Anhui MedicalUniversity, Hefei 230601, Anhui, China[8]Department of Biochemistry,University of New Mexico, Albuquerque NM 87131, NM, USA[9]Department ofGenetics, and Renaissance Computing Institute, University of North Carolinaat Chapel Hill, Chapel Hill, NC 27517, USA[10]Department of Dermatology,China-Japan Friendship Hospital, Beijing 100029, China[11]Department ofDermatology, University of Michigan Medical School, Ann Arbor, MI 48109,USA[12]Department of Biostatistics, Center for Statistical Genetics, Universityof Michigan, Ann Arbor, MI 48109, USA[13]Department of ComputationalMedicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109,USA
Background: 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. Methods: 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. Results: 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-corrected P < 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 of C1orf106, the TSS1500 promoter region of DMBX1 and the body of SIK3. Conclusions: 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.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31100908, 81370044, 81130031, 81273301]
第一作者单位：[1]Institute and Department of Dermatology, The First Affiliated Hospital,Anhui Medical University, Meishan Road 81, Hefei 230032, Anhui Province,China[2]The Key Laboratory of Dermatology, Ministry of Education, AnhuiMedical University, Anhui, China[3]Collaborative Innovation Center forComplex and Severe Dermatosis, Anhui Medical University, Hefei 230032,Anhui, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute and Department of Dermatology, The First Affiliated Hospital,Anhui Medical University, Meishan Road 81, Hefei 230032, Anhui Province,China[2]The Key Laboratory of Dermatology, Ministry of Education, AnhuiMedical University, Anhui, China[3]Collaborative Innovation Center forComplex and Severe Dermatosis, Anhui Medical University, Hefei 230032,Anhui, China[7]Department of Dermatology, The Second Affiliated Hospital, Anhui MedicalUniversity, Hefei 230601, Anhui, China
推荐引用方式(GB/T 7714)：
Fusheng Zhou,Changbing Shen,Jingkai Xu,et al.Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis[J].CLINICAL EPIGENETICS.2016,8:doi:10.1186/s13148-016-0297-z.
APA：
Fusheng Zhou,Changbing Shen,Jingkai Xu,Jing Gao,Xiaodong Zheng...&Xuejun Zhang.(2016).Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis.CLINICAL EPIGENETICS,8,
MLA：
Fusheng Zhou,et al."Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis".CLINICAL EPIGENETICS 8.(2016)
