Understanding the genetic and epigenetic basis of common variable immunodeficiency disorder through omics approaches.
Common variable immunodeficiency disorder (CVID) is the most frequently encountered symptomatic primary immunodeficiency, characterized by highly heterogeneous immunological features and clinical presentations. As better targeted therapies are importantly needed for CVID, improved understanding of the genetic and epigenetic basis for the development of CVID presents the most promising venue for improvement.



Several genomic and epigenomic studies of CVID have recently been carried out on cohorts of sporadic cases of CVID. Using high-throughput array and sequencing technologies, these studies identified several loci associated with the disease. Here, we review the omics approaches used in these studies and resulting discoveries. We also discuss how these findings lead to improved understanding of the molecular basis of CVID and possible future directions to pursue.



High-throughput omics approaches have been productive in genetic and epigenetic studies of CVID, leading to the identifications of several significantly associated loci of different variant types, as well as genes and pathways elucidating the shared genetic basis of CVID and autoimmunity. Complex polygenic model of inheritance together with interplay between genetic components and environmental factors may account for the etiology of CVID and various associated comorbidities.



The genetic and epigenetic basis of CVID when further translated through functional studies will allow for improved understanding of the CVID etiology and will provide new insights into the development of potential new therapeutic approaches for this devastating condition. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.
Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Jin
J
Li
Department of Computer Science, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: zhiwei04@gmail.com.
Zhi
Z
Wei
Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA; Medical Scientist Training Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yun R
YR
Li
Department of Immunology, Landspitali University Hospital, Hringbraut (building 14 at Eiriksgata), 101 Reykjavik, Iceland.
S Melkorka
SM
Maggadottir
Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Xiao
X
Chang
Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Akshatha
A
Desai
Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Hakon
H
Hakonarson
D017074:Common Variable Immunodeficiency / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D057890:Epigenomics / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans
Common variable immunodeficiency disorder; Copy number variation; Epigenetic; Genome-wide association study; Meta-analysis