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Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We conducted a GWAS on the indices of IR (HOMA2-IR) and beta cell function (HOMA2-%B) in 6,217 non-diabetic individuals from the Qatar Biobank (QBB; Discovery cohort; n = 2170, Replication cohort; n = 4047) with and without body mass index (BMI) adjustment. We also developed polygenic scores (PGS) for HOMA2-IR and compared their performance with a previously derived PGS for HOMA-IR (PGS003470). We replicated 11 loci that have been previously associated with HOMA-IR and 24 loci that have been associated with HOMA-%B, at nominal statistical significance. We also identified a novel locus associated with beta cell function near VEGFC gene, tagged by rs61552983 (P = 4.38 × 10-8). Moreover, our best performing PGS (Q-PGS4; Adj R2 = 0.233 ± 0.014; P = 1.55 x 10-3) performed better than PGS003470 (Adj R2 = 0.194 ± 0.014; P = 5.45 x 10-2) in predicting HOMA2-IR in our dataset. This is the first GWAS on HOMA2 and the first GWAS conducted in the Middle East focusing on IR and beta cell function. Herein, we report a novel locus in VEGFC that is implicated in beta cell dysfunction. Inclusion of under-represented populations in GWAS has potentials to provide important insights into the genetic architecture of IR and beta cell function.

Background: Graft-versus-host disease (GVHD) continues to emerge as the topmost causative factor of the morbidity and mortality rate post hematopoietic stem cell transplantation. The graft cells attack the recipient host tissues resulting in acute or chronic GVHD that affect organs, including the lung, liver, skin, and gastrointestinal tract. Certain factors are considered to play a crucial role in the progression of the disease, such as antibodies produced by B cells, reduction in regulatory T cells, and immune tolerance disruption to self-antigen. Main body: This review highlighted the pathophysiology of GVHD, clinical manifestation, stages of GVHD in different organs, and the significant role played by Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) in cytokine signalling, development, and function of several immune cells. Furthermore, we discussed the clinical efficacy of drugs, which comprises JAK inhibitors, monoclonal antibodies, and proteasome inhibitors that are widely used to treat GVHD. Conclusion: Considering the progress recorded in identifying the therapeutic regimens for GVHD, novel and effective therapeutic approaches are much needed to alleviate the complication that arises post hematopoietic stem cell transplantation and reduce the morbidity and mortality rate of the disease.