SUPR
Genetic and immunological comparisons of rheumatic diseases among Sudanese and Swedish patients
Dnr:

sens2021587

Type:

SNIC SENS

Principal Investigator:

Johan Rönnelid

Affiliation:

Uppsala universitet

Start Date:

2021-10-25

End Date:

2025-11-01

Primary Classification:

30107: Medical Genetics

Allocation

Abstract

Background This collaborative project between Sudan and Sweden was initiated in 2008, and Sudanese patients with rheumatoid arthritis (RA), Systemic Lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) have been recruited in Khartoum, Sudan and compared with Swedish cohorts from Karolinska Institutet (KI) and Gävle with the same diagnoses. These projects have so far concerned clinical and immunological comparisons, and formed the scientific basis for two doctoral theses in our group (2013, 2020). The obtained immunological and clinical data will be utilized in the currently planned studies which have an immunogenetic focus. We have obtained ample genome-wide association study (GWAS) for the Sudanese cohorts, performed by Science for Life Laboratory (SciLife Lab) using the Infinium Expanded Multi-Ethnic genotyping array (MegaEx) at Uppsala university. These data are ready to download when we get our own Bianca project. The Swedish cohorts have data on HLA-DRB1* and Immunochip version 1. These data will also be exported to the same Bianca project. We are planning to include OLINK proteomics on the Sudanese cohorts, results from which will be used as expression data (QTL analyses) and also be compared with the available OLINK data from Swedish patients. OLINK data will be added to the Bianca project in the future. MegaEx analyses of Sudanese patients were obtained in 2016, and a new GDPR-compliant ethical clearance has been obtained (Dnr 2021-01137, dated 2021-03-29). The PUBA for transfer of genetic and clinical data from KI to the common computer area at Bianca was completed with all signatures on 2021-10-04. Aims The aim is to explore these Sudanese-Swedish comparative genetic data in relation to the already obtained clinical and autoimmune characteristics from our previous studies plus pending Olink analyses. The genetic studies will include imputation of HLA genes (with help from reference files from African populations included in the 1000 genomes project), conventional SNP analyses of genes associated with SLE and APS and RA and QTL analyses. Methodology Data will be stored on the Bianca server where access will be granted to the PI and two scientist who will be conducting the analyses (post doc Sahwa Elbagir MD PhD at UU, and bioinformatician Lina Diaz-Gallo PhD at KI). The prevalence of SNPs will be compared between cases and controls in each country. Frequencies of HLA alleles and SNPs will be related to quantifiable clinical variables such as disease activity and to biomarkers e.g. autoantibodies and cytokines measured with Olink technology. Significance Patients with identical rheumatic diagnoses in Sudan and Sweden differ both concerning genes and environmental factors driving the occurrence and severity of disease. Our Sudanese RA and SLE/APS cohorts are unique and well characterized, they represent until now very little investigated East African rheumatic populations. This interdisciplinary project will describe the genetic and pathophysiological background of patients with major inflammatory rheumatic diseases from East Africa using standardized methodology, therefore, delivering knowledge and expanding understanding of RA and SLE in previously under-investigated populations.