Transcriptome-wide association study identifies new susceptibility genes and pathways for spondyloarthritis
Abstract Background Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear. Methods...
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Published in | Journal of orthopaedic surgery and research Vol. 18; no. 1; pp. 1 - 659 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
London
BioMed Central Ltd
04.09.2023
BioMed Central BMC |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Background
Spondyloarthritis (SpA) is a group of multifactorial bone diseases influenced by genetic factors, the environment and lifestyle. However, current studies have found a limited number of SpA-related genes, and the genetic and pathogenic mechanisms of SpA are still unclear.
Methods
A tissue-specific transcriptome-wide association study (TWAS) of SpA was performed using GWAS (including 3966 SpA patients and 448,298 controls) summary data and gene expression weights of whole blood and skeletal muscle. The SpA-associated genes identified by TWAS were further compared with the differentially expressed genes (DEGs) identified in the SpA gene expression profile acquired from the Gene Expression Omnibus database (GEO, GSE58667). Finally, functional enrichment and annotation analyses of the identified genes were performed.
Results
The TWAS detected 499 suggestive genes associated with SpA in whole blood and skeletal muscle, such as
CTNNAL1
(
P
SM
= 3.04 × 10
−2
,
P
WB
= 9.58 × 10
−3
). The gene expression profile of SpA identified 20 candidate genes that overlapped in the TWAS data, such as
MCM4
(
P
TWAS
= 1.32 × 10
−2
,
P
DEG
= 2.75 × 10
−2
) and
KIAA1109
(
P
TWAS
= 3.71 × 10
−2
,
P
DEG
= 4.67 × 10
−2
). Enrichment analysis of the genes identified by TWAS identified 93 significant GO terms and 33 KEGG pathways, such as mitochondrion organization (GO: 0007005) and axon guidance (hsa04360).
Conclusion
We identified multiple candidate genes that were genetically related to SpA. Our study may provide novel clues regarding the genetic mechanism, diagnosis, and treatment of SpA. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1749-799X 1749-799X |
DOI: | 10.1186/s13018-023-04029-4 |