GENETIC DETERMINANTS OF INSULIN RESISTANCE IN THE MIDDLE EASTERN QATARI POPULATION

Abstract

Type 2 diabetes (T2D) is a life-threatening metabolic disorder that profoundly affects life quality, economy, and mortality. It is majorly driven by insulin resistance (IR) and concurrent beta cell dysfunction. Here, we analyzed the deep phenotypic data of 14,395 Qatar Biobank (QBB) participants and described their diabetes status and the prevalence of insulin resistance. We also conducted genome-wide association studies (GWAS) on insulin resistance (HOMA2-IR) and beta cell function (HOMA2-%B) on 2,170 individuals of the QBB first batch. The GWAS was adjusted for sex, age, BMI, and the first ten principal components. SNPs that reached a p-value < 5 x 10-5 were carried forward for replication in another 4,047 individuals of second batch of QBB. Results revealed that of the 14,395 QBB participants, 20.2% (n = 2,910) have type 2 diabetes, 0.5% (n = 77) have type 1 diabetes, and 62.5% (n = 8,999) are normal (non-diabetics). Of the non-diabetics, more than 30% of them are already insulin resistant. We did not identify any novel loci implicated in IR or beta cell function in the Qatari population. However, we replicated all the previously reported loci associated with IR or beta cell function at p-value < 0.05, including the strongest and most consistent signals. Also, the strongest SNP reported to be associated with beta cell function rs10830963 around MTNR1B has shown a significant association which was even further strengthened after adjusting for BMI. Comparison of effect sizes and allele frequency have shown notable differences between QGP and the five super populations of the 1000 genome project. The study underscores the necessity to conduct more population-specific studies with large datasets to aid in understanding and appreciating the diversities across populations.

Date of Award	2023
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences