Epigenome-wide analysis of sperm cells identifies IL22 as a possible germ line risk locus for psoriatic arthritis

Psoriasis and its associated inflammatory arthritis, psoriatic arthritis (PsA), have a clear heritable component, but a large proportion of the heritable risk remains unexplained by gene sequence variation. This study aimed to determine if epigenetic factors contribute to the missing heritability in...

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Bibliographic Details
Published in:PloS one 2019-02, Vol.14 (2), p.e0212043
Main Authors: Pollock, Remy A, Zaman, Laila, Chandran, Vinod, Gladman, Dafna D
Format: Article
Language:English
Subjects:
Adult
Age of Onset
Aged
Arthritis
Arthritis, Psoriatic - genetics
Biology and life sciences
Case-Control Studies
Copy number
CpG Islands
Criminal investigation
Cytokines
Deoxyribonucleic acid
Dermatologic agents
Disease
DNA
DNA fingerprinting
DNA Methylation
EDTA
Environmental factors
Epigenetic inheritance
Epigenetics
Epigenomics - methods
Gene expression
Genes
Genetic aspects
Genetic Predisposition to Disease
Genomes
Genotyping
Germ cells
Health care networks
Heritability
High-Throughput Nucleotide Sequencing
Humans
Inflammation
Interleukin 22
Interleukins - genetics
Joint diseases
Joints (anatomy)
Male
Medicine
Medicine and Health Sciences
Methylation
Middle Aged
Physical Sciences
Psoriasis
Psoriatic arthritis
Rheumatic diseases
Rheumatology
Sequence Analysis, DNA
Skin
Skin diseases
Sperm
Spermatozoa - chemistry
Studies
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Summary:Psoriasis and its associated inflammatory arthritis, psoriatic arthritis (PsA), have a clear heritable component, but a large proportion of the heritable risk remains unexplained by gene sequence variation. This study aimed to determine if epigenetic factors contribute to the missing heritability in psoriatic disease. DNA methylation profiling was performed on sperm cells from 23 probands with psoriasis without PsA (PsC), 13 PsA probands, and 18 unaffected controls. Differentially methylated CpGs and regions (DMRs) were identified and validated by pyrosequencing. Underlying AluY and copy number variation (CNV) in the HCG26 and IL22 genes, respectively, were assessed by genotyping. Array, subject's age, age of psoriasis onset, psoriasis severity, and medication usage were found to influence methylation at many genes and were included as covariates in the analysis. Between PsC probands vs. controls, 169 DMRs were found; 754 DMRs were found between PsA probands vs. controls, and 86 between PsA and PsC probands (adjusted p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0212043