Abstract
Despite dedicated nation-wide efforts to raise awareness against the harmful effects of fast-food consumption and sedentary lifestyle, the Arab population continues to struggle with an increased risk for metabolic disorders. Unlike the European population, the Arab population lacks well-established genetic risk determinants for metabolic disorders, and the transferability of established risk loci to this population has not been satisfactorily demonstrated. The most recent findings have identified over 240 genetic risk loci (with ~400 independent association signals) for type 2 diabetes, but thus far only 25 risk loci (ADAMTS9, ALX4, BCL11A, CDKAL1, CDKN2A/B, COL8A1, DUSP9, FTO, GCK, GNPDA2, HMG20A, HNF1A, HNF1B, HNF4A, IGF2BP2, JAZF1, KCNJ11, KCNQ1, MC4R, PPARγ, SLC30A8, TCF7L2, TFAP2B, TP53INP1, and WFS1) have been replicated in Arab populations. To our knowledge, large-scale population- or family-based association studies are non-existent in this region. Recently, we conducted genome-wide association studies on Arab individuals from Kuwait to delineate the genetic determinants for quantitative traits associated with anthropometry, lipid profile, insulin resistance, and blood pressure levels. Although these studies led to the identification of novel recessive variants, they failed to reproduce the established loci. However, they provided insights into the genetic architecture of the population, the applicability of genetic models based on recessive mode of inheritance, the presence of genetic signatures of inbreeding due to the practice of consanguinity, and the pleiotropic effects of rare disorders on complex metabolic disorders. This perspective presents analysis strategies and study designs for identifying genetic risk variants associated with diabetes and related traits in Arab populations.
Highlights
Discovery of oil reserves in the Arabian Gulf since the 1930s increased overall wealth in these countries
Published reports on T2DM genetics in the Arab population originate from Kuwait, Lebanon, Saudi Arabia, Qatar, UAE, Oman, and Tunisia (Table 1)
The optimum sample size is determined by various factors including homogeneity seen in the population, prevalence of the disorder, variance in the trait measurements, genetic models used in the association tests, number of markers tested in the study, allele frequencies of the risk variants, effect sizes, genome control inflation rates, desired Type I error rates, type of study design [71, 72]
Summary
Discovery of oil reserves in the Arabian Gulf since the 1930s increased overall wealth in these countries. Rapid socioeconomic transitions in Arab countries in the rich post-oil era marked changes in the nutritional patterns and food habits, including a shift from locally grown natural products to a Western diet and change from nomadic way to urbanized life These resulted in an increasingly sedentary lifestyle and wide-spread obesity [1,2,3] and an increased prevalence of. Published reports on T2DM genetics in the Arab population originate from Kuwait, Lebanon, Saudi Arabia, Qatar, UAE, Oman, and Tunisia (Table 1) Some of these studies illustrate certain overlaps with established T2DM risk loci, some illustrate the complete absence of any overlap (Table 1), and some identify novel risk loci. This is underlined by the following observations in the Arab population: the prevalence of obesity in T2DM patients is high [41], Arab
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