Mapping rheumatoid arthritis susceptibility through integrative bioinformatics and genomics

Nining Medi Sushanti (Faculty of Pharmacy, Universitas Ahmad Dahlan)
Wirawan Adikusuma (Departement of Pharmacy, University of Muhammadiyah Mataram, Mataram Research Center for Vaccine and Drugs, National Research and Innovation Agency (BRIN), South Tangerang)
Arief Rahman Afief (Faculty of Pharmacy, Universitas Ahmad Dahlan)
Anita Silas La’ah (Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei,Taiwan)
Firdayani Firdayani (Research Center for Vaccine and Drugs, National Research and Innovation Agency (BRIN), South Tangerang)
Rockie Chong (Department of Chemistry and Biochemistry, University of California, Los Angeles, USA)
Zainul Amiruddin Zakaria (Borneo Research on Algesia, Inflammation and Neurodegeneration (BRAIN) Group, Department of Biomedical Sciences, Faculty of Medicines and Health Sciences, University Malaysia Sabah)
Barkah Djaka Purwanto (Faculty of Medicine, Universitas Ahmad Dahlan PKU Muhammadiyah Bantul Hospital, Bantul)
Rahmat Dani Satria (Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281 Clinical Laboratory Installation, Dr. Sardjito Central General Hospital, Yogyakarta 55281)
Riat Khair (Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281 Clinical Laboratory Installation, Dr. Sardjito Central General Hospital, Yogyakarta 55281)
Abdi Wira Septama (Traditional Medicine, National Research and Innovation Agency (BRIN), South Tangerang,)
Lalu Muhammad Irham (Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta Traditional Medicine, National Research and Innovation Agency (BRIN), South Tangerang)

Media Farmasi : Jurnal Ilmu Farmasi (Journal Of Pharmaceutical Science)
Vol 20, No 1: March 2023

Rheumatoid arthritis (RA) is an autoimmune disease that influences several organs and tissues, especially the synovial joints, and is associated with multiple genetic and environmental factors. Numerous databases provide information on the relationship between a specific gene and the disease pathogenesis. However, it is important to further prioritize biological risk genes for downstream development and validation.  This study aims to map RA-association genetic variation using genome-wide association study (GWAS) databases and prioritize influential genes in RA pathogenesis based on functional annotations. These functional annotations include missense/nonsense mutations, cis-expression quantitative trait locus (cis-eQTL), overlap knockout mouse phenotype (KMP), protein-protein interaction (PPI), molecular pathway analysis (MPA), and primary immunodeficiency (PID). 119 genetic variants mapped had a potential high risk for RA based on functional scoring. The top eight risk genes of RA are TYK2 and IFNGR2, followed by TNFRSF1A, IL12RB1 and CD40, C5, NCF2, and IL6R. These candidate genes are potential biomarkers for RA that can aid drug discovery and disease diagnosis.