title: cepip: context-dependent epigenomic weighting for prioritization of regulatory variants and disease-associated genes.
abstract: It remains challenging to predict regulatory variants in particular tissues or cell types due to highly context-specific gene regulation. By connecting large-scale epigenomic profiles to expression quantitative trait loci (eQTLs) in a wide range of human tissues/cell types, we identify critical chromatin features that predict variant regulatory potential. We present cepip, a joint likelihood framework, for estimating a variant's regulatory probability in a context-dependent manner. Our method exhibits significant GWAS signal enrichment and is superior to existing cell type-specific methods. Furthermore, using phenotypically relevant epigenomes to weight the GWAS single-nucleotide polymorphisms, we improve the statistical power of the gene-based association test.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China. mulin0424.li@gmail.com.|Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China. mulin0424.li@gmail.com.|Department of Statistics, Harvard University, Cambridge, Boston, MA, 02138-2901, USA. mulin0424.li@gmail.com.
authors.forename: Mulin Jun
authors.initials: MJ
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, Center for Genome Research, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.|Centre for Reproduction, Development and Growth, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Li
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Dingge
authors.initials: D
authors.lastname: Ying
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Health Sciences Research & Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, 85259, USA.
authors.forename: Panwen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Health Sciences Research & Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, 85259, USA.
authors.forename: Jean-Pierre A
authors.initials: JA
authors.lastname: Kocher
authors.affiliation: Department of Anaesthesiology, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Centre for Genomic Sciences, The University of Hong Kong, Hong Kong SAR, China.|Department of Psychiatry, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Department of Statistics, Harvard University, Cambridge, Boston, MA, 02138-2901, USA. jliu@stat.harvard.edu.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Liu
authors.affiliation: Department of Health Sciences Research & Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ, 85259, USA. wang.junwen@mayo.edu.|Department of Biomedical Informatics, Arizona State University, Scottsdale, AZ, 85259, USA. wang.junwen@mayo.edu.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
mesh_terms: D002843:Chromatin / Q000235:genetics; D016000:Cluster Analysis; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D015870:Gene Expression; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D006657:Histones / Q000378:metabolism; D006801:Humans; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D002843:Chromatin; D006657:Histones
keywords: Cell type-specific; Disease-susceptible gene; Epigenome; Regulatory variant; Variant prioritization