Deciphering Kawasaki disease genetics through next-generation sequencing: A scoping review
Abstract
BACKGROUND: Kawasaki disease (KD) is an acute self-limiting childhood vasculitis. KD is considered the most common cause of acquired heart disease in children worldwide. Despite being the leading cause of acquired heart disease in children, its etiology remains poorly understood. Several epidemiological studies reveal a strong genetic predisposition to KD susceptibility, underlying coronary artery abnormalities (CAAs) and treatment resistance to intravenous immunoglobulin (IVIG).
AIM: To evaluate the current literature on the roles of targeted next-generation sequencing (NGS), whole-exome sequencing (WES) and/or whole-genome sequencing (WGS) in identifying genetic susceptibility loci, immunopathogenic pathways, and mechanisms of IVIG resistance in KD.
METHODS: We performed a literature search to identify key genes and pathways associated with genetic susceptibility, IVIG resistance, and CAAs development in KD. Our search was conducted across PubMed, Scopus, and Google Scholar. Studies investigating these features using targeted NGS, WES or WGS were included in this review. Studies employing other methods to investigate genetic susceptibility, IVIG resistance, and CAA among KD patients were excluded.
RESULTS: Targeted NGS, WES and WGS studies of the KD cohort across different regions have identified both rare and common variants associated with KD-related phenotypes. Genes with these variants were linked to immune regulation and vascular biology. Genes linked with innate and adaptive immune responses included TLR6, MEF2A, HLA-DRB1, IL6ST, MYH14, RBP3, EFCC1, FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10. Studies have also revealed genes associated with CAA. These genes were IL17RC, FGFR4, IL31RA, FNDC1, MMP8, and FOXN1, all of which were implicated in inflammatory and vascular remodelling processes. WGS studies also identified novel loci associated with IVIG resistance. These were FANK1, MAP2K3, KCNJ12, CA10, CWH43, EDN1, PPP2R5E, and SFMBT2, as well as previously established genes such as ITPKC, CASP3, FCGR2A, CD40, and IL1B. Many of these genes have known or proposed functions in biological pathways potentially relevant to KD, including TLR and NF-κB signalling, IL-17-mediated cytokine pathways, calcium/NFAT signalling, MAPK signalling, vascular remodelling, and endothelial dysfunction. Moreover, sex-biased variants (EFCC1, LMO7, CEMIP, and USH2A) also revealed gender-based differences in KD susceptibility, indicating a higher risk of KD in boys.
CONCLUSION: Studies using NGS-based approaches have significantly advanced understanding of KD by identifying key candidate genes and pathways associated with disease susceptibility, CAAs, and IVIG response, and IVIG resistance. These findings support a multi-pathway immunovascular model of KD. Future studies involving larger, ethnically diverse cohorts and functional validation are essential for clinical translation.
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BibTeX
@article{kumar2026deciphering,
title = {{Deciphering Kawasaki disease genetics through next-generation sequencing: A scoping review}},
author = {Anoop Kumar and Vaishali Thakur and Manpreet Dhaliwal and Taranpreet Kaur and Khem Raj and Jayakanthan Kabeerdoss and Amit Rawat and Rakesh Kumar Pilania},
journal = {World Journal of Clinical Pediatrics},
year = {2026},
month = nov,
doi = {10.5409/wjcp.122059},
url = {https://doi.org/10.5409/wjcp.122059},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Deciphering Kawasaki disease genetics through next-generation sequencing: A scoping review
AU - Anoop Kumar
AU - Vaishali Thakur
AU - Manpreet Dhaliwal
AU - Taranpreet Kaur
AU - Khem Raj
AU - Jayakanthan Kabeerdoss
AU - Amit Rawat
AU - Rakesh Kumar Pilania
PY - 2026
DA - 2026/11/03
JO - World Journal of Clinical Pediatrics
DO - 10.5409/wjcp.122059
UR - https://doi.org/10.5409/wjcp.122059
AB - BACKGROUND: Kawasaki disease (KD) is an acute self-limiting childhood vasculitis. KD is considered the most common cause of acquired heart disease in children worldwide. Despite being the leading cause of acquired heart disease in children, its etiology remains poorly understood. Several epidemiological studies reveal a strong genetic predisposition to KD susceptibility, underlying coronary artery abnormalities (CAAs) and treatment resistance to intravenous immunoglobulin (IVIG). AIM: To evaluate the current literature on the roles of targeted next-generation sequencing (NGS), whole-exome sequencing (WES) and/or whole-genome sequencing (WGS) in identifying genetic susceptibility loci, immunopathogenic pathways, and mechanisms of IVIG resistance in KD. METHODS: We performed a literature search to identify key genes and pathways associated with genetic susceptibility, IVIG resistance, and CAAs development in KD. Our search was conducted across PubMed, Scopus, and Google Scholar. Studies investigating these features using targeted NGS, WES or WGS were included in this review. Studies employing other methods to investigate genetic susceptibility, IVIG resistance, and CAA among KD patients were excluded. RESULTS: Targeted NGS, WES and WGS studies of the KD cohort across different regions have identified both rare and common variants associated with KD-related phenotypes. Genes with these variants were linked to immune regulation and vascular biology. Genes linked with innate and adaptive immune responses included TLR6, MEF2A, HLA-DRB1, IL6ST, MYH14, RBP3, EFCC1, FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10. Studies have also revealed genes associated with CAA. These genes were IL17RC, FGFR4, IL31RA, FNDC1, MMP8, and FOXN1, all of which were implicated in inflammatory and vascular remodelling processes. WGS studies also identified novel loci associated with IVIG resistance. These were FANK1, MAP2K3, KCNJ12, CA10, CWH43, EDN1, PPP2R5E, and SFMBT2, as well as previously established genes such as ITPKC, CASP3, FCGR2A, CD40, and IL1B. Many of these genes have known or proposed functions in biological pathways potentially relevant to KD, including TLR and NF-κB signalling, IL-17-mediated cytokine pathways, calcium/NFAT signalling, MAPK signalling, vascular remodelling, and endothelial dysfunction. Moreover, sex-biased variants (EFCC1, LMO7, CEMIP, and USH2A) also revealed gender-based differences in KD susceptibility, indicating a higher risk of KD in boys. CONCLUSION: Studies using NGS-based approaches have significantly advanced understanding of KD by identifying key candidate genes and pathways associated with disease susceptibility, CAAs, and IVIG response, and IVIG resistance. These findings support a multi-pathway immunovascular model of KD. Future studies involving larger, ethnically diverse cohorts and functional validation are essential for clinical translation.
SN - 2219-2808
ER -