title: Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus.
abstract: We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells' findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10(-6)), CD14+ monocytes (P ≤ 2.74 × 10(-4)) and CD19+ B cells (P ≤ 2.00 × 10(-6)), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10(-6)). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10(-44)) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE.
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China Department of Genetics, The Renaissance Computing Institute, University of North Carolina at Chapel Hill, North Carolina 27517.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Wen
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Changbing
authors.initials: C
authors.lastname: Shen
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Yinjuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Dermatology, Ministry of Education, State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, 230032, China Key Laboratory of Gene Resource Utilization for Complex Diseases, Hefei, Anhui Province, 230032, China Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, Anhui Province, 230032, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, China-Japan Friendship Hospital, Beijing, 100029, China wuhucuiyong@vip.163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
mesh_terms: D016000:Cluster Analysis; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D015398:Signal Transduction
keywords: Genetics of Immunity; SNPsea; genome-wide association studies; systemic lupus erythematosus