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Updated: Jun 26, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Genetic Rare Variants Affecting Multiple Pathways in Japanese Patients with Palindromic Rheumatism
Taketo Kawara1, Koji Inoue2, Shunichi Shiozawa3
1Division of Medical Biophysics, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Abstract:
Palindromic rheumatism (PR) is a type of cryptogenic paroxysmal arthritis. Several genes may be involved in PR pathogenesis; however, conducting comprehensive case-control genetic studies for PR poses challenges owing to its rarity as a disease. Moreover, case-control studies may overlook rare variants that occur infrequently but play a significant role in pathogenesis. This study aimed to identify disease-related genes in Japanese patients with PR using whole-genome sequencing (WGS) and rare-variant analysis. Genomic DNA was obtained from two familial cases and one sporadic case, and it was subjected to WGS. WGS data of 104 healthy individuals obtained from a public database were used as controls. We performed data analysis for rare variants on detected variants using SKAT-O, KBAC, and SKAT, and subsequently defined significant genes. Significant genes combined with variants shared between the cases were defined as disease-related genes. We also performed pathway analysis for disease-related genes using Reactome. We identified 2,695,244 variants shared between cases; after excluding polymorphisms and noise, 74,640 variants were detected. We identified 540 disease-related genes, including 1,893 variants. Furthermore, we identified 32 significant pathways. Our results indicate that the detected genes and pathways in this study may be involved in PR pathogenesis.
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